1.
Protein phosphorylation
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Protein phosphorylation is a post-translational modification of proteins in which an amino acid residue is phosphorylated by a protein kinase by the addition of a covalently bound phosphate group. Phosphorylation alters the conformation of a protein, causing it to become activated, deactivated. The reverse reaction of phosphorylation is called dephosphorylation, and is catalyzed by protein phosphatases, protein kinases and phosphatases work independently and in a balance to regulate the function of proteins. However, many amino acids can also be phosphorylated, including arginine, lysine. Protein phosphorylation was first reported in 1906 by Phoebus Levene at the Rockefeller Institute for Medical Research with the discovery of phosphorylated vitellin, however, it was nearly 50 years until the enzymatic phosphorylation of proteins by protein kinases was discovered. In 1906, Phoebus Levene at the Rockefeller Institute for Medical Research identified phosphate in the protein vitellin, however, it took another 20 years before Eugene P. Kennedy described the first ‘enzymatic phosphorylation of proteins’. The first phosphorylase enzyme was discovered by Carl and Gerty Cori in the late 1930s, Carl and Gerty Cori found two forms of glycogen phosphorylase which they named A and B but did not correctly understand the mechanism of the B form to A form conversion. Protein phosphatase 1 is able to catalyze the dephosphorylation of phosphorylated enzymes by removing the phosphate group, earl Sutherland explained in 1950, that the activity of phosphorylase was increased and thus glycogenolysis stimulated when liver slices were incubated with adrenalin and glucagon. Also in the 1970s, the term multisite phosphorylation was coined in response to the discovery of proteins that are phosphorylated on two or more residues by two or more kinases, in 1975, it was shown that cAMP-dependent proteins kinases phosphorylate serine residues on specific amino acid sequence motifs. Ray Erikson discovered that v-Src was a kinase and Tony Hunter found that v-Src phosphorylated tyrosine residues on proteins in the 1970s, in the early 1980, the amino-acid sequence of the first protein kinase was determined which helped geneticists understand the functions of regulatory genes. Edmond Fisher and Edwin Krebs were awarded the Nobel prize in 1992 “for their discoveries concerning reversible protein phosphorylation as a biological regulatory mechanism”. Phosphorylation introduces a charged and hydrophilic group in the chain of amino acids. Some proteins such as p53 contain multiple sites, facilitating complex. Arginine phosphorylation by McsB kinase marks proteins for degradation by a Clp protease, the arginine phosphorylation system, which is widely distributed across Gram-positive bacteria, appears to be functionally analogous to the eukaryotic ubiquitin–proteasome system. The first example of regulation by phosphorylation was glycogen phosphorylase. Eddie Fisher and Ed Krebs described how phosphorylation of glycogen phosphorylase b converted it to the glycogen phosphorylase a. It was soon discovered that glycogen synthase, another enzyme, is inactivated by phosphorylation. Phosphorylation of the enzyme GSK-3 by AKT as part of the signaling pathway
2.
Serine
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Serine encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC is an ɑ-amino acid that is used in the biosynthesis of proteins. It contains a group, a carboxyl group, and a side chain consisting of a hydroxymethyl group. It can be synthesized in the body under normal physiological circumstances. This compound is one of the naturally occurring amino acids. Only the L-stereoisomer appears naturally in proteins and it is not essential to the human diet, since it is synthesized in the body from other metabolites, including glycine. Serine was first obtained from silk protein, a rich source. Its name is derived from the Latin for silk, sericum, serines structure was established in 1902. The biosynthesis of serine starts with the oxidation of 3-phosphoglycerate to 3-phosphohydroxypyruvate, reductive amination of this ketone by phosphoserine transaminase yields 3-phosphoserine which is hydrolyzed to serine by phosphoserine phosphatase. In bacteria such as E. coli these enzymes are encoded by the genes serA, serC, glycine biosynthesis, Serine hydroxymethyltransferase also catalyzes the reversible conversions of L-serine to glycine and 5,6,7, 8-tetrahydrofolate to 5, 10-methylenetetrahydrofolate. SHMT is a pyridoxal phosphate dependent enzyme, glycine can also be formed from CO2, NH4+, and mTHF in a reaction catalyzed by glycine synthase. Industrially, L-serine is produced by fermentation, with an estimated 100-1000 tonnes per year produced, in the laboratory, racemic serine can be prepared from methyl acrylate via several steps, Serine is important in metabolism in that it participates in the biosynthesis of purines and pyrimidines. It is the precursor to several amino acids including glycine and cysteine and it is also the precursor to numerous other metabolites, including sphingolipids and folate, which is the principal donor of one-carbon fragments in biosynthesis. Serine plays an important role in the function of many enzymes. It has been shown to occur in the sites of chymotrypsin, trypsin. Serine sidechains are often bonded, the commonest small motifs formed are ST turns, ST motifs. As a constituent of proteins, its side chain can undergo O-linked glycosylation and it is one of three amino acid residues that are commonly phosphorylated by kinases during cell signaling in eukaryotes. Phosphorylated serine residues are often referred to as phosphoserine, Serine proteases are a common type of protease. D-Serine, synthesized in the brain by serine racemase from L-serine, serves as a neuromodulator by coactivating NMDA receptors, D-serine is a potent agonist at the glycine site of the NMDA-type glutamate receptor
3.
Chemistry
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Chemistry is a branch of physical science that studies the composition, structure, properties and change of matter. Chemistry is sometimes called the science because it bridges other natural sciences, including physics. For the differences between chemistry and physics see comparison of chemistry and physics, the history of chemistry can be traced to alchemy, which had been practiced for several millennia in various parts of the world. The word chemistry comes from alchemy, which referred to a set of practices that encompassed elements of chemistry, metallurgy, philosophy, astrology, astronomy, mysticism. An alchemist was called a chemist in popular speech, and later the suffix -ry was added to this to describe the art of the chemist as chemistry, the modern word alchemy in turn is derived from the Arabic word al-kīmīā. In origin, the term is borrowed from the Greek χημία or χημεία and this may have Egyptian origins since al-kīmīā is derived from the Greek χημία, which is in turn derived from the word Chemi or Kimi, which is the ancient name of Egypt in Egyptian. Alternately, al-kīmīā may derive from χημεία, meaning cast together, in retrospect, the definition of chemistry has changed over time, as new discoveries and theories add to the functionality of the science. The term chymistry, in the view of noted scientist Robert Boyle in 1661, in 1837, Jean-Baptiste Dumas considered the word chemistry to refer to the science concerned with the laws and effects of molecular forces. More recently, in 1998, Professor Raymond Chang broadened the definition of chemistry to mean the study of matter, early civilizations, such as the Egyptians Babylonians, Indians amassed practical knowledge concerning the arts of metallurgy, pottery and dyes, but didnt develop a systematic theory. Greek atomism dates back to 440 BC, arising in works by such as Democritus and Epicurus. In 50 BC, the Roman philosopher Lucretius expanded upon the theory in his book De rerum natura, unlike modern concepts of science, Greek atomism was purely philosophical in nature, with little concern for empirical observations and no concern for chemical experiments. Work, particularly the development of distillation, continued in the early Byzantine period with the most famous practitioner being the 4th century Greek-Egyptian Zosimos of Panopolis. He formulated Boyles law, rejected the four elements and proposed a mechanistic alternative of atoms. Before his work, though, many important discoveries had been made, the Scottish chemist Joseph Black and the Dutchman J. B. English scientist John Dalton proposed the theory of atoms, that all substances are composed of indivisible atoms of matter. Davy discovered nine new elements including the alkali metals by extracting them from their oxides with electric current, british William Prout first proposed ordering all the elements by their atomic weight as all atoms had a weight that was an exact multiple of the atomic weight of hydrogen. The inert gases, later called the noble gases were discovered by William Ramsay in collaboration with Lord Rayleigh at the end of the century, thereby filling in the basic structure of the table. Organic chemistry was developed by Justus von Liebig and others, following Friedrich Wöhlers synthesis of urea which proved that organisms were, in theory
4.
Dephosphorylation
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Dephosphorylation is the removal of a phosphate group from an organic compound by hydrolysis. It is a reversible post-translational modification, dephosphorylation and its counterpart, phosphorylation, activate and deactivate enzymes by detaching or attaching phosphoric esters and anhydrides. A notable occurrence of dephosphorylation is the conversion of ATP to ADP, dephosphorylation employs a type of hydrolytic enzyme, or hydrolase, which cleave ester bonds. The prominent hydrolase subclass used in dephosphorylation is phosphatase, phosphatase removes phosphate groups by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group. The reversible phosphorylation-dephosphorylation reaction occurs in every physiological process, making proper function of protein phosphases necessary for organism viability, because protein dephosphorylation is a key process involved in cell signalling, protein phosphatases are implicated in conditions such as cardiac disease, diabetes, and Alzheimers disease. The discovery of dephosphorylation came from a series of experiments examining the enzyme phosphorylase isolated from rabbit skeletal muscle. In 1955, Edwin Krebs and Edmond Fischer used radiolabeled ATP to determine that phosphate is added to the residue of phosphorylase to convert it from its b to a form via phosphorylation. Subsequently, Krebs and Fischer showed that this phosphorylation is part of a kinase cascade, finally, after purifying the phosphorylated form of the enzyme, phosphorylase a, from rabbit liver, ion exchange chromatography was used to identify phosphoprotein phosphatase I and II. Edwin Krebs and Edmond Fischer won the 1992 Nobel Prize in Physiology or Medicine for the discovery of reversible protein phosphorylation, phosphorylation involves the covalent modification of the hydroxyl with a phosphate group through the nucleophilic attack of the alpha phosphate in ATP by the oxygen in the hydroxyl. Dephosphorylation involves removal of the group through a hydration reaction by addition of a molecule of water and release of the original phosphate group. Both processes are reversible and either mechanism can be used to activate or deactivate a protein, phosphorylation of a protein produces many biochemical effects, such as changing its conformation to alter its binding to a specific ligand to increase or reduce its activity. Phosphorylation and dephosphorylation can be used on all types of substrates, such as proteins, enzymes, membrane channels, signaling molecules. The sum of these processes is referred to as phosphoregulation, the deregulation of phosphorylation can lead to disease. During the synthesis of proteins, polypeptide chains, which are created by ribosomes translating mRNA, the dephosphorylation of proteins is a mechanism for modifying behavior of a protein, often by activating or inactivating an enzyme. Components of the protein synthetic apparatus also undergo phosphorylation and dephosphorylation, as part of postranslational modifications, phosphate groups may be removed from serine, threonine, or tyrosine. As such, pathways of signal transduction depend on sequential phosphorylation and dephosphorylation of a wide variety of proteins. ATP4− + H2O --> ADP3− + HPO42− + H+ Adenosine triphosphate, or ATP, in a spontaneous dephosphorylation reaction 30.5 kJ/mol is released, which is harnessed to drive cellular reactions. Overall, nonspontaneous reactions coupled to the dephosphorylation of ATP are spontaneous and this is important in driving oxidative phosphorylation
5.
Biology
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Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, evolution, distribution, identification and taxonomy. Modern biology is a vast and eclectic field, composed of branches and subdisciplines. However, despite the broad scope of biology, there are certain unifying concepts within it that consolidate it into single, coherent field. In general, biology recognizes the cell as the unit of life, genes as the basic unit of heredity. It is also understood today that all organisms survive by consuming and transforming energy and by regulating their internal environment to maintain a stable, the term biology is derived from the Greek word βίος, bios, life and the suffix -λογία, -logia, study of. The Latin-language form of the term first appeared in 1736 when Swedish scientist Carl Linnaeus used biologi in his Bibliotheca botanica, the first German use, Biologie, was in a 1771 translation of Linnaeus work. In 1797, Theodor Georg August Roose used the term in the preface of a book, karl Friedrich Burdach used the term in 1800 in a more restricted sense of the study of human beings from a morphological, physiological and psychological perspective. The science that concerns itself with these objects we will indicate by the biology or the doctrine of life. Although modern biology is a recent development, sciences related to. Natural philosophy was studied as early as the ancient civilizations of Mesopotamia, Egypt, the Indian subcontinent, however, the origins of modern biology and its approach to the study of nature are most often traced back to ancient Greece. While the formal study of medicine back to Hippocrates, it was Aristotle who contributed most extensively to the development of biology. Especially important are his History of Animals and other works where he showed naturalist leanings, and later more empirical works that focused on biological causation and the diversity of life. Aristotles successor at the Lyceum, Theophrastus, wrote a series of books on botany that survived as the most important contribution of antiquity to the plant sciences, even into the Middle Ages. Scholars of the medieval Islamic world who wrote on biology included al-Jahiz, Al-Dīnawarī, who wrote on botany, biology began to quickly develop and grow with Anton van Leeuwenhoeks dramatic improvement of the microscope. It was then that scholars discovered spermatozoa, bacteria, infusoria, investigations by Jan Swammerdam led to new interest in entomology and helped to develop the basic techniques of microscopic dissection and staining. Advances in microscopy also had a impact on biological thinking. In the early 19th century, a number of biologists pointed to the importance of the cell. Thanks to the work of Robert Remak and Rudolf Virchow, however, meanwhile, taxonomy and classification became the focus of natural historians
6.
Enzyme
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Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase
7.
Protein
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Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, a linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide, short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides, or sometimes oligopeptides. The individual amino acid residues are bonded together by peptide bonds, the sequence of amino acid residues in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the code specifies 20 standard amino acids, however. Sometimes proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors, proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes. Once formed, proteins only exist for a period of time and are then degraded and recycled by the cells machinery through the process of protein turnover. A proteins lifespan is measured in terms of its half-life and covers a wide range and they can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal and or misfolded proteins are degraded more rapidly due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms, many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized, digestion breaks the proteins down for use in the metabolism. Methods commonly used to study structure and function include immunohistochemistry, site-directed mutagenesis, X-ray crystallography, nuclear magnetic resonance. Most proteins consist of linear polymers built from series of up to 20 different L-α-amino acids, all proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this structure as it contains an unusual ring to the N-end amine group. The amino acids in a chain are linked by peptide bonds. Once linked in the chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen. The peptide bond has two forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar
8.
Eukaryote
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A eukaryote is any organism whose cells contain a nucleus and other organelles enclosed within membranes. Eukaryotes belong to the taxon Eukarya or Eukaryota, the presence of a nucleus gives eukaryotes their name, which comes from the Greek εὖ and κάρυον. Eukaryotic cells also contain other membrane-bound organelles such as mitochondria and the Golgi apparatus, in addition, plants and algae contain chloroplasts. Eukaryotic organisms may be unicellular or multicellular, only eukaryotes form multicellular organisms consisting of many kinds of tissue made up of different cell types. Eukaryotes can reproduce asexually through mitosis and sexually through meiosis and gamete fusion. In mitosis, one cell divides to produce two identical cells. In meiosis, DNA replication is followed by two rounds of division to produce four daughter cells each with half the number of chromosomes as the original parent cell. These act as sex cells resulting from genetic recombination during meiosis, the domain Eukaryota appears to be monophyletic, and so makes up one of the three domains of life. The two other domains, Bacteria and Archaea, are prokaryotes and have none of the above features, eukaryotes represent a tiny minority of all living things. However, due to their larger size, eukaryotes collective worldwide biomass is estimated at about equal to that of prokaryotes. Eukaryotes first developed approximately 1. 6–2.1 billion years ago, in 1905 and 1910, the Russian biologist Konstantin Mereschkowsky argued three things about the origin of nucleated cells. Firstly, plastids were reduced cyanobacteria in a symbiosis with a non-photosynthetic host, secondly, the host had earlier in evolution formed by symbiosis between an amoeba-like host and a bacteria-like cell that formed the nucleus. Thirdly, plants inherited photosynthesis from cyanobacteria, the split between the prokaryotes and eukaryotes was introduced in the 1960s. The concept of the eukaryote has been attributed to the French biologist Edouard Chatton, the terms prokaryote and eukaryote were more definitively reintroduced by the Canadian microbiologist Roger Stanier and the Dutch-American microbiologist C. B. van Niel in 1962. In his 1938 work Titres et Travaux Scientifiques, Chatton had proposed the two terms, calling the bacteria prokaryotes and organisms with nuclei in their cells eukaryotes. However he mentioned this in one paragraph, and the idea was effectively ignored until Chattons statement was rediscovered by Stanier. In 1967, Lynn Margulis provided microbiological evidence for endosymbiosis as the origin of chloroplasts and mitochondria in cells in her paper. In the 1970s, Carl Woese explored microbial phylogenetics, studying variations in 16S ribosomal RNA and this helped to uncover the origin of the eukaryotes and the symbiogenesis of two important eukaryote organelles, mitochondria and chloroplasts
9.
Lipid
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In biology, lipids comprise a group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins, monoglycerides, diglycerides, triglycerides, phospholipids, and others. The main biological functions of lipids include storing energy, signaling, lipids have applications in the cosmetic and food industries as well as in nanotechnology. Biological lipids originate entirely or in part from two types of biochemical subunits or building-blocks, ketoacyl and isoprene groups. Although the term lipid is sometimes used as a synonym for fats, fats are a subgroup of lipids called triglycerides, lipids also encompass molecules such as fatty acids and their derivatives, as well as other sterol-containing metabolites such as cholesterol. Although humans and other mammals use various biosynthetic pathways both to break down and to synthesize lipids, some essential lipids cannot be made this way, the word lipid stems etymologically from the Greek lipos. The fatty acid structure is one of the most fundamental categories of biological lipids, the carbon chain, typically between four and 24 carbons long, may be saturated or unsaturated, and may be attached to functional groups containing oxygen, halogens, nitrogen, and sulfur. If a fatty acid contains a double bond, there is the possibility of either a cis or trans geometric isomerism, cis-double bonds cause the fatty acid chain to bend, an effect that is compounded with more double bonds in the chain. This in turn plays an important role in the structure and function of cell membranes, most naturally occurring fatty acids are of the cis configuration, although the trans form does exist in some natural and partially hydrogenated fats and oils. Examples of biologically important fatty acids include the eicosanoids, derived primarily from arachidonic acid and eicosapentaenoic acid, that include prostaglandins, leukotrienes, docosahexaenoic acid is also important in biological systems, particularly with respect to sight. Other major lipid classes in the fatty acid category are the fatty esters, fatty esters include important biochemical intermediates such as wax esters, fatty acid thioester coenzyme A derivatives, fatty acid thioester ACP derivatives and fatty acid carnitines. The fatty amides include N-acyl ethanolamines, such as the cannabinoid neurotransmitter anandamide, glycerolipids are composed of mono-, di-, and tri-substituted glycerols, the best-known being the fatty acid triesters of glycerol, called triglycerides. The word triacylglycerol is sometimes used synonymously with triglyceride, in these compounds, the three hydroxyl groups of glycerol are each esterified, typically by different fatty acids. Because they function as a store, these lipids comprise the bulk of storage fat in animal tissues. The hydrolysis of the bonds of triglycerides and the release of glycerol. Additional subclasses of glycerolipids are represented by glycosylglycerols, which are characterized by the presence of one or more sugar residues attached to glycerol via a glycosidic linkage, examples of structures in this category are the digalactosyldiacylglycerols found in plant membranes and seminolipid from mammalian sperm cells. Glycerophospholipids, usually referred to as phospholipids, are ubiquitous in nature and are key components of the bilayer of cells, as well as being involved in metabolism. Neural tissue contains high amounts of glycerophospholipids, and alterations in their composition has been implicated in various neurological disorders. Examples of glycerophospholipids found in biological membranes are phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine, the major sphingoid base of mammals is commonly referred to as sphingosine
10.
Post-translational modification
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Post-translational modification refers to the covalent and generally enzymatic modification of proteins during or after protein biosynthesis. Proteins are synthesized by ribosomes translating mRNA into polypeptide chains, which may then undergo PTM to form the protein product. PTMs are important components in cell signaling, post-translational modifications can occur on the amino acid side chains or at the proteins C- or N- termini. They can extend the chemical repertoire of the 20 standard amino acids by modifying an existing functional group or introducing a new one such as phosphate, phosphorylation is a very common mechanism for regulating the activity of enzymes and is the most common post-translational modification. Attachment of lipid molecules, known as lipidation, often targets a protein or part of an attached to the cell membrane. Other forms of post-translational modification consist of cleaving peptide bonds, as in processing a propeptide to a form or removing the initiator methionine residue. The formation of bonds from cysteine residues may also be referred to as a post-translational modification. Some types of modification are consequences of oxidative stress. Carbonylation is one example that targets the modified protein for degradation, specific amino acid modifications can be used as biomarkers indicating oxidative damage. In addition, although the amide of asparagine is a weak nucleophile, rarer modifications can occur at oxidized methionines and at some methylenes in side chains. Post-translational modification of proteins can be detected by a variety of techniques, including mass spectrometry, Eastern blotting. O-acylation, N-acylation, S-acylation acetylation, the addition of an acetyl group, formylation alkylation, the addition of an alkyl group, e. g. methyl, ethyl methylation the addition of a methyl group, usually at lysine or arginine residues. Formed by oxidative dissociation of a C-terminal Gly residue, amide bond formation amino acid addition arginylation, a tRNA-mediation addition polyglutamylation, covalent linkage of glutamic acid residues to the N-terminus of tubulin and some other proteins. Distinct from glycation, which is regarded as an attachment of sugars. Glycation, the addition of a molecule to a protein without the controlling action of an enzyme. Carbamylation the addition of Isocyanic acid to a proteins N-terminus or the side-chain of Lys. carbonylation the addition of carbon monoxide to other organic/inorganic compounds, biotinylation, covalent attachment of a biotin moiety using a biotinylation reagent, typically for the purpose of labeling a protein. Carbamylation, the addition of Isocyanic acid to a proteins N-terminus or the side-chain of Lys or Cys residues, oxidation, addition of one or more Oxygen atoms to a susceptible side-chain, principally of Met, Trp, His or Cys residues. Formation of disulfide bonds between Cys residues, pegylation, covalent attachment of polyethylene glycol using a pegylation reagent, typically to the N-terminus or the side-chains of Lys residues
11.
Threonine
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Threonine encoded by the codons ACU, ACC, ACA, and ACG is an α-amino acid that is used in the biosynthesis of proteins. It contains a group, an α-carboxylic acid group. It is essential in humans, meaning the body cannot synthesize it, threonine is synthesized from aspartate in bacteria such as E. coli. Threonine sidechains are often bonded, the commonest small motifs formed are ST turns, ST motifs. The threonine residue is susceptible to numerous posttranslational modifications, the hydroxyl side-chain can undergo O-linked glycosylation. In addition, threonine residues undergo phosphorylation through the action of a threonine kinase, in its phosphorylated form, it can be referred to as phosphothreonine. It is a precursor of glycine, and can be used as a prodrug to reliably elevate brain glycine levels, threonine was discovered as the last of the 20 common proteinogenic amino acids in 1935s by William Cumming Rose, collaborating with Curtis Meyer and William Rose. Threonine can exist in four possible stereoisomers with the following configurations, however, the name L-threonine is used for one single diastereomer, -2-amino-3-hydroxybutanoic acid. The second stereoisomer, which is present in nature, is called L-allo-threonine. The two stereoisomers - and -2-amino-3-hydroxybutanoic acid are only of minor importance, as an essential amino acid, threonine is not synthesized in humans, hence we must ingest threonine in the form of threonine-containing proteins. In plants and microorganisms, threonine is synthesized from aspartic acid via α-aspartyl-semialdehyde, homoserine undergoes O-phosphorylation, this phosphate ester undergoes hydrolysis concomitant with relocation of the OH group. Enzymes involved in a typical biosynthesis of threonine include, aspartokinase β-aspartate semialdehyde dehydrogenase homoserine dehydrogenase homoserine kinase threonine synthase, threonine is metabolized in two ways, It is converted to pyruvate via threonine dehydrogenase. An intermediate in this pathway can undergo thiolysis with CoA to produce acetyl-CoA, in humans, it is converted to α-ketobutyrate. This is the pathway for threonine degradation. The mechanism of the first step is analogous to that catalyzed by serine dehydratase, foods high in threonine include cottage cheese, poultry, fish, meat, lentils, Black turtle bean and Sesame seeds. Racemic threonine can be prepared from crotonic acid by using mercury acetate. Threonine biosynthesis CID205 CID6288
12.
Tyrosine
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Tyrosine or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is an amino acid with a polar side group. Its codons are UAC and UAU, the word tyrosine is from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese. It is called tyrosyl when referred to as a group or side chain. Aside from being an amino acid, tyrosine has a special role by virtue of the phenol functionality. It occurs in proteins that are part of signal transduction processes and it functions as a receiver of phosphate groups that are transferred by way of protein kinases. Phosphorylation of the group changes the activity of the target protein. A tyrosine residue plays a important role in photosynthesis. In chloroplasts, it acts as a donor in the reduction of oxidized chlorophyll. In this process, it loses the hydrogen atom of its phenolic OH-group and this radical is subsequently reduced in the photosystem II by the four core manganese clusters. The Recommended Dietary Allowance for phenylalanine and tyrosine is 33 mg per kilogram of body weight, for a 70 kg person this is 2310 mg. For example, the white of an egg has about 250 mg per egg, in plants and most microorganisms, tyr is produced via prephenate, an intermediate on the shikimate pathway. Mammals synthesize tyrosine from the amino acid phenylalanine, which is derived from food. The conversion of phe to tyr is catalyzed by the enzyme phenylalanine hydroxylase and this enzyme catalyzes the reaction causing the addition of a hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine, such that it becomes tyrosine. Some of the residues can be tagged with a phosphate group by protein kinases. In its phosphorylated form, tyrosine is called phosphotyrosine, tyrosine phosphorylation is considered to be one of the key steps in signal transduction and regulation of enzymatic activity. Phosphotyrosine can be detected through specific antibodies, tyrosine residues may also be modified by the addition of a sulfate group, a process known as tyrosine sulfation. Tyrosine sulfation is catalyzed by tyrosylprotein sulfotransferase, like the phosphotyrosine antibodies mentioned above, antibodies have recently been described that specifically detect sulfotyrosine
13.
Phosphodiester bond
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A phosphodiester bond occurs when exactly two of the hydroxyl groups in phosphoric acid react with hydroxyl groups on other molecules to form two ester bonds. Phosphodiester bonds are central to all life on Earth, as make up the backbone of the strands of nucleic acid. In DNA and RNA, the bond is the linkage between the 3 carbon atom of one sugar molecule and the 5 carbon atom of another, deoxyribose in DNA. Strong covalent bonds form between the group and two 5-carbon ring carbohydrates over two ester bonds. The phosphate groups in the bond are negatively charged. Because the phosphate groups have a pKa near 0, they are charged at pH7. This repulsion forces the phosphates to take opposite sides of the DNA strands and is neutralized by proteins, metal ions such as magnesium, when a single phosphate or two phosphates known as pyrophosphates break away and catalyze the reaction, the phosphodiester bond is formed. Hydrolysis of phosphodiester bonds can be catalyzed by the action of phosphodiesterases which play an important role in repairing DNA sequences, the phosphodiester linkage between two ribonucleotides can be broken by alkaline hydrolysis, whereas the linkage between two deoxyribonucleotides is more stable under these conditions. The relative ease of RNA hydrolysis is an effect of the presence of the 2 hydroxyl group, a phosphodiesterase is an enzyme that catalyzes the hydrolysis of phosphodiester bonds, for instance a bond in a molecule of cyclic AMP or cyclic GMP. An enzyme that plays an important role in the repair of oxidative DNA damage is the 3-phosphodiesterase, during the replication of DNA, there is a hole between the phosphates in the backbone left by DNA polymerase I. DNA ligase is able to form a bond between the nucleotides. Phosphodiesterase Phosphodiesterase inhibitor DNA replication, DNA, ATP Teichoic acid, DNase I PDE5 Nick
14.
Histidine
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Histidine is an α-amino acid that is used in the biosynthesis of proteins. It contains a group, a carboxylic acid group. Initially thought essential only for infants, longer-term studies have shown it is essential for adults also, Histidine was first isolated by German physician Albrecht Kossel and Sven Hedin in 1896. It is also a precursor to histamine, an inflammatory agent in immune responses. The conjugate acid of the side chain in histidine has a pKa of approximately 6.0. This means that, at physiologically relevant pH values, relatively small shifts in pH will change its average charge, below a pH of 6, the imidazole ring is mostly protonated as described by the Henderson–Hasselbalch equation. When protonated, the ring bears two NH bonds and has a positive charge. The positive charge is distributed between both nitrogens and can be represented with two equally important resonance structures. As the pH increases past approximately 6, one of the protons is lost, the remaining proton of the now-neutral imidazole ring can reside on either nitrogen, giving rise to what are known as the N1-H or N3-H tautomers. When both imidazole ring nitrogens are protonated, their 15N chemical shifts are similar, NMR shows that the chemical shift of N1-H drops slightly, whereas the chemical shift of N3-H drops considerably. This indicates that the N1-H tautomer is preferred, it is presumed due to hydrogen bonding to the neighboring ammonium, as the pH rises above 9, the chemical shifts of N1 and N3 become approximately 185 and 170 ppm. An entirely deprotonated form of the ring, the imidazolate ion, would be formed only above a pH of 14. This change in chemical shifts can be explained by the presumably decreased hydrogen bonding of an amine over an ammonium ion, and this should act to decrease the N1-H tautomer preference. The imidazole ring of histidine is aromatic at all pH values and it contains six pi electrons, four from two double bonds and two from a nitrogen lone pair. It can form pi stacking interactions, but is complicated by the positive charge and it does not absorb at 280 nm in either state, but does in the lower UV range more than some amino acids. The imidazole sidechain of histidine is a coordinating ligand in metalloproteins and is a part of catalytic sites in certain enzymes. It has the ability to switch between protonated and unprotonated states, which allows histidine to participate in acid-base catalysis, in catalytic triads, the basic nitrogen of histidine is used to abstract a proton from serine, threonine, or cysteine to activate it as a nucleophile. In a histidine proton shuttle, histidine is used to quickly shuttle protons and it can do this by abstracting a proton with its basic nitrogen to make a positively charged intermediate and then use another molecule, a buffer, to extract the proton from its acidic nitrogen
15.
Lysine
–
Lysine, encoded by the codons AAA and AAG, is an α-amino acid that is used in the biosynthesis of proteins. It contains a group, an α-carboxylic acid group. It is essential in humans, meaning the body cannot synthesize it, lysine is a base, as are arginine and histidine. The ε-amino group often participates in hydrogen bonding and as a base in catalysis. The ε-amino group is attached to the carbon from the α-carbon. O-Glycosylation of hydroxylysine residues in the endoplasmic reticulum or Golgi apparatus is used to mark certain proteins for secretion from the cell, deficiencies may cause blindness, as well as many other problems due to its ubiquitous presence in proteins. As an essential amino acid, lysine is not synthesized in animals, in plants and most bacteria, it is synthesized from aspartic acid, L-aspartate is first converted to L-aspartyl-4-phosphate by aspartokinase. ATP is needed as a source for this step. β-Aspartate semialdehyde dehydrogenase converts this into β-aspartyl-4-semialdehyde, energy from NADPH is used in this conversion. 4-hydroxy-tetrahydrodipicolinate synthase adds a pyruvate group to the β-aspartyl-4-semialdehyde, and a molecule is removed. This causes cyclization and gives rise to -4-hydroxy-2,3,4 and this product is reduced to 2,3,4, 5-tetrahydrodipicolinate by 4-hydroxy-tetrahydrodipicolinate reductase. This reaction consumes an NADPH molecule and releases a water molecule. Tetrahydrodipicolinate N-acetyltransferase opens this ring and gives rise to N-succinyl-L-2-amino-6-oxoheptanedionate, two water molecules and one acyl-CoA enzyme are used in this reaction. This reaction is catalyzed by the enzyme succinyl diaminopimelate aminotransferase, a glutamic acid molecule is used in this reaction and an oxoacid is produced as a byproduct. N-succinyl-LL-2, 6-diaminoheptanedionate is converted into LL-2, 6-diaminoheptanedionate by succinyl diaminopimelate desuccinylase, a water molecule is consumed in this reaction and a succinate is produced a byproduct. LL-2, 6-diaminoheptanedionate is converted by diaminopimelate epimerase into meso-2, 6-diamino-heptanedionate, finally, meso-2, 6-diamino-heptanedionate is converted into L-lysine by diaminopimelate decarboxylase. It is worth noting, however, that in fungi, euglenoids, lysine is metabolised in mammals to give acetyl-CoA, via an initial transamination with α-ketoglutarate. The bacterial degradation of lysine yields cadaverine by decarboxylation, allysine is a derivative of lysine, used in the production of elastin and collagen
16.
Aspartic acid
–
Aspartic acid, also known as aspartate, is an α-amino acid that is used in the biosynthesis of proteins. Similar to all other amino acids it contains an amino group and its α-amino group is in the protonated –NH+3 form under physiological conditions, while its α-carboxylic acid group is deprotonated −COO− under physiological conditions. Aspartic acid has a side chain which reacts with other amino acids, enzymes. Under physiological conditions in proteins the side chain usually occurs as the negatively charged aspartate form and it is a non-essential amino acid in humans, meaning the body can synthesize it as needed. D-Aspartate is one of two D-amino acids commonly found in mammals, in proteins aspartate sidechains are often hydrogen bonded, often as asx turns or asx motifs, which often occur at the N-termini of alpha helices. Asps L-isomer is one of the 22 proteinogenic amino acids, i. e. the building blocks of proteins. Asp is classified as acidic, with a pKa of 3.9, however in a peptide this is dependent on the local environment. Aspartic acid was first discovered in 1827 by Auguste-Arthur Plisson and Étienne Ossian Henry by hydrolysis of asparagine and their original method used lead hydroxide, but various other acids or bases are more commonly used instead. There are two forms or enantiomers of aspartic acid, the name aspartic acid can refer to either enantiomer or a mixture of two. Of these two forms, only one, L-aspartic acid, is incorporated into proteins. The biological roles of its counterpart, D-aspartic acid are more limited, where enzymatic synthesis will produce one or the other, most chemical syntheses will produce both forms, DL-aspartic acid, known as a racemic mixture. Because Aspartate can be synthesized by the body it is classified as an amino acid. In the human body, aspartate is most frequently synthesized through the transamination of oxaloacetate, the biosynthesis of aspartate is facilitated by an aminotransferase enzyme, the transfer of an amine group from another molecule such as alanine or glutamine yields aspartate and an alpha-keto acid. Aspartate is also a byproduct of the urea cycle, racemic aspartic acid can be synthesized from diethyl sodium phthalimidomalonate. The major disadvantage of the technique is that equimolar amounts of each enantiomer are made. Using biotechnology it is now possible to use immobilised enzymes to create just one type of enantiomer owing to their stereospecificity. In plants and microorganisms, aspartate is the precursor to several amino acids, including four that are essential for humans, methionine, threonine, isoleucine, the conversion of aspartate to these other amino acids begins with reduction of aspartate to its semialdehyde, O2CCHCH2CHO. Asparagine is derived from aspartate via transamidation, -O2CCHCH2CO2- + GCNH3+ O2CCHCH2CONH3+ + GCO In the urea cycle, aspartate, Aspartate has many other biochemical roles
17.
Glutamic acid
–
Glutamic acid is an α-amino acid with formula C 5H 9O 4N. It is usually abbreviated as Glu or E in biochemistry and its molecular structure could be idealized as HOOC-CH-2-COOH, with two carboxyl groups -COOH and one amino group -NH2. However, in the state and mildly acid water solutions. Glutamic acid is used by almost all living beings in the biosynthesis of proteins and it is non-essential in humans, meaning the body can synthesize it. The acid can lose one proton from second carboxyl group to form the conjugate base and this form of the compound is prevalent in neutral solutions. The glutamate neurotransmitter plays the role in neural activation. This anion is also responsible for the flavor of certain foods. In highly alkaline solutions the doubly negative anion −OOC-CH-2-COO− prevails, the radical corresponding to glutamate is called glutamyl. When glutamic acid is dissolved in water, the group may gain a proton, and/or the carboxyl groups may lose protons. In sufficiently acid environments, the group gains a proton. At pH values between about 2.5 and 4.1, the carboxylic acid closer to the amine generally loses a proton, and the acid becomes the neutral zwitterion −OOC-CH-2-COOH. This is also the form of the compound in the solid state. The switchover is gradual, the two forms are in equal concentrations at pH2.10, at even higher pH, the other carboxyl loses its proton and the acid exists almost entirely as the glutamate anion −OOC-CH-2-COO−, with a single negative charge. The switchover occurs at pH4.07, the latter is the case, in particular, in the physiological pH range. At even higher pH, the group loses the extra proton. The switchover occurs at pH9.47, the carbon atom adjacent to the amino group is chiral, so glutamic acid can exist in two optical isomers, D and L. The L form is the one most widely occurring in nature, but the D form occurs in special contexts, such as the cell walls of the bacterium Escherichia coli. Although they occur naturally in foods, the flavor contributions made by glutamic acid
18.
Organic acid anhydride
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An organic acid anhydride is an acid anhydride that is an organic compound. An acid anhydride is a compound that has two acyl groups bonded to the oxygen atom. A common type of acid anhydride is a carboxylic anhydride, where the parent acid is a carboxylic acid. Symmetrical acid anhydrides of this type are named by replacing the word acid in the name of the parent carboxylic acid by the word anhydride, thus, 2O is called acetic anhydride. Mixed acid anhydrides, such as acetic anhydride, are known. One or both groups of an acid anhydride may also be derived from another type of organic acid. One of the groups of an acid anhydride can be derived from an inorganic acid such as phosphoric acid. The mixed anhydride 1, 3-bisphosphoglycerate is an intermediate in the formation of ATP via glycolysis, is the mixed anhydride between 3-phosphoglyceric acid and phosphoric acid, acidic oxides are often classified as acid anhydrides. Acid anhydrides are prepared in industry by diverse means, Acetic anhydride is mainly produced by the carbonylation of methyl acetate. Maleic anhydride is produced by the oxidation of benzene or butane, laboratory routes emphasize the dehydration of the corresponding acids. In reactions with protic substrates, the reactions afford equal amounts of the acylated product, acid anhydrides tend to be less electrophilic than acyl chlorides, and only one acyl group is transferred per molecule of acid anhydride, which leads to a lower atom efficiency. The low cost, however, of acetic anhydride makes it a choice for acetylation reactions. Illustrative acid anhydrides Acetic anhydride is an industrial chemical widely used for preparing acetate esters. Maleic anhydride is the precursor to various resins by copolymerization with styrene, maleic anhydride is a dienophile in the Diels-Alder reaction. Dianhydrides, molecules containing two acid anhydride functions, are used to synthesize polyimides and sometimes polyesters and polyamides, polyanhydrides are a class of polymers characterized by anhydride bonds that connect repeat units of the polymer backbone chain. Natural organic acid anhydrides are rare, because of the reactivity of the functional group, examples include cantharidin from species of blister beetle, including the Spanish fly, Lytta vesicatoria, and tautomycin, from the bacterium Streptomyces spiroverticillatus. Sulfur can replace oxygen, either in the group or in the bridge. In the former case, the name of the group is enclosed in parentheses to avoid ambiguity in the name
19.
Biochemistry
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Biochemistry, sometimes called biological chemistry, is the study of chemical processes within and relating to living organisms. By controlling information flow through biochemical signaling and the flow of energy through metabolism. Biochemistry is closely related to biology, the study of the molecular mechanisms by which genetic information encoded in DNA is able to result in the processes of life. Depending on the definition of the terms used, molecular biology can be thought of as a branch of biochemistry, or biochemistry as a tool with which to investigate. The chemistry of the cell depends on the reactions of smaller molecules. These can be inorganic, for water and metal ions, or organic, for example the amino acids. The mechanisms by which cells harness energy from their environment via chemical reactions are known as metabolism, the findings of biochemistry are applied primarily in medicine, nutrition, and agriculture. In medicine, biochemists investigate the causes and cures of diseases, in nutrition, they study how to maintain health and study the effects of nutritional deficiencies. In agriculture, biochemists investigate soil and fertilizers, and try to discover ways to improve crop cultivation, crop storage and pest control. However, biochemistry as a scientific discipline has its beginning sometime in the 19th century, or a little earlier. Gowland Hopkins on enzymes and the nature of biochemistry. The term biochemistry itself is derived from a combination of biology, the German chemist Carl Neuberg however is often cited to have coined the word in 1903, while some credited it to Franz Hofmeister. Then, in 1828, Friedrich Wöhler published a paper on the synthesis of urea and these techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle. Another significant historic event in biochemistry is the discovery of the gene and this part of biochemistry is often called molecular biology. In the 1950s, James D. Watson, Francis Crick, Rosalind Franklin, in 1958, George Beadle and Edward Tatum received the Nobel Prize for work in fungi showing that one gene produces one enzyme. In 1988, Colin Pitchfork was the first person convicted of murder with DNA evidence, mello received the 2006 Nobel Prize for discovering the role of RNA interference, in the silencing of gene expression. Around two dozen of the 92 naturally occurring elements are essential to various kinds of biological life. Most rare elements on Earth are not needed by life, while a few common ones are not used, most organisms share element needs, but there are a few differences between plants and animals
20.
Sugar
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Sugar is the generic name for sweet, soluble carbohydrates, many of which are used in food. There are various types of derived from different sources. Simple sugars are called monosaccharides and include glucose, fructose, the table sugar or granulated sugar most customarily used as food is sucrose, a disaccharide of glucose and fructose. Sugar is used in prepared foods and it is added to some foods, in the body, sucrose is hydrolysed into the simple sugars fructose and glucose. Other disaccharides include maltose from malted grain, and lactose from milk, longer chains of sugars are called oligosaccharides or polysaccharides. Some other chemical substances, such as glycerol may also have a sweet taste, low-calorie food substitutes for sugar, described as artificial sweeteners, include aspartame and sucralose, a chlorinated derivative of sucrose. Sugars are found in the tissues of most plants and are present in sufficient concentrations for efficient commercial extraction in sugarcane, the world production of sugar in 2011 was about 168 million tonnes. The average person consumes about 24 kilograms of sugar each year, equivalent to over 260 food calories per person, since the latter part of the twentieth century, it has been questioned whether a diet high in sugars, especially refined sugars, is good for human health. Sugar has been linked to obesity, and suspected of, or fully implicated as a cause in the occurrence of diabetes, cardiovascular disease, dementia, macular degeneration, the etymology reflects the spread of the commodity. The English word sugar ultimately originates from the Sanskrit शर्करा, via Arabic سكر as granular or candied sugar, the contemporary Italian word is zucchero, whereas the Spanish and Portuguese words, azúcar and açúcar, respectively, have kept a trace of the Arabic definite article. The Old French word is zuchre and the contemporary French, sucre, the earliest Greek word attested is σάκχαρις. The English word jaggery, a brown sugar made from date palm sap or sugarcane juice, has a similar etymological origin – Portuguese jagara from the Sanskrit शर्करा. Sugar has been produced in the Indian subcontinent since ancient times and it was not plentiful or cheap in early times and honey was more often used for sweetening in most parts of the world. Originally, people chewed raw sugarcane to extract its sweetness, sugarcane was a native of tropical South Asia and Southeast Asia. Different species seem to have originated from different locations with Saccharum barberi originating in India and S. edule, one of the earliest historical references to sugarcane is in Chinese manuscripts dating back to 8th century BC that state that the use of sugarcane originated in India. Sugar was found in Europe by the 1st century AD, but only as an imported medicine and it is a kind of honey found in cane, white as gum, and it crunches between the teeth. It comes in lumps the size of a hazelnut, sugar is used only for medical purposes. Sugar remained relatively unimportant until the Indians discovered methods of turning sugarcane juice into granulated crystals that were easier to store, crystallized sugar was discovered by the time of the Imperial Guptas, around the 5th century AD
21.
Catabolism
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Catabolism is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy, or used in other anabolic reactions. Catabolism breaks down molecules into smaller units. Cells use the monomers released from breaking down polymers to construct new polymer molecules, or degrade the monomers further to simple waste products. Cellular wastes include lactic acid, acetic acid, carbon dioxide, ammonia and this molecule acts as a way for the cell to transfer the energy released by catabolism to the energy-requiring reactions that make up anabolism. Catabolism therefore provides the energy necessary for the maintenance and growth of cells. There are many signals that control catabolism, most of the known signals are hormones and the molecules involved in metabolism itself. Endocrinologists have traditionally classified many of the hormones as anabolic or catabolic, the so-called classic catabolic hormones known since the early 20th century are cortisol, glucagon, and adrenaline. In recent decades, many more hormones with at least some catabolic effects have been discovered, including cytokines, orexin, many of these catabolic hormones express an anti-catabolic effect in muscle tissue. One study found that the administration of epinephrine had an anti-proteolytic effect, another study found that catecholamines in general, greatly decreased the rate of muscle catabolism. Autophagy Dehydration synthesis Hydrolysis Nocturnal post absorptive catabolism Psilacetin § Pharmacology Sarcopenia Media related to Catabolism at Wikimedia Commons
22.
Glycolysis
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Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+. The free energy released in this process is used to form the high-energy molecules ATP, glycolysis is a determined sequence of ten enzyme-catalyzed reactions. The intermediates provide entry points to glycolysis, for example, most monosaccharides, such as fructose and galactose, can be converted to one of these intermediates. The intermediates may also be directly useful, for example, the intermediate dihydroxyacetone phosphate is a source of the glycerol that combines with fatty acids to form fat. Glycolysis is an oxygen independent metabolic pathway, meaning that it not use molecular oxygen for any of its reactions. However the products of glycolysis are sometimes metabolized using atmospheric oxygen, when molecular oxygen is used for the metabolism of the products of glycolysis the process is usually referred to as aerobic, whereas if no oxygen is used the process is said to be anaerobic. Thus, glycolysis occurs, with variations, in all organisms. The wide occurrence of glycolysis indicates that it is one of the most ancient metabolic pathways, glycolysis could thus have originated from chemical constraints of the prebiotic world. Glycolysis occurs in most organisms in the cytosol of the cell, the most common type of glycolysis is the Embden–Meyerhof–Parnas, which was discovered by Gustav Embden, Otto Meyerhof, and Jakub Karol Parnas. Glycolysis also refers to other pathways, such as the Entner–Doudoroff pathway, however, the discussion here will be limited to the Embden–Meyerhof–Parnas pathway. The overall reaction of glycolysis is, The use of symbols in this equation makes it appear unbalanced with respect to oxygen atoms, hydrogen atoms, and charges. In the cellular environment, all three groups of ADP dissociate into −O− and H+, giving ADP3−, and this ion tends to exist in an ionic bond with Mg2+. ATP behaves identically except that it has four groups, giving ATPMg2−. When these differences along with the charges on the two phosphate groups are considered together, the net charges of −4 on each side are balanced. For simple fermentations, the metabolism of one molecule of glucose to two molecules of pyruvate has a net yield of two molecules of ATP, most cells will then carry out further reactions to repay the used NAD+ and produce a final product of ethanol or lactic acid. Many bacteria use inorganic compounds as hydrogen acceptors to regenerate the NAD+, cells performing aerobic respiration synthesize much more ATP, but not as part of glycolysis. These further aerobic reactions use pyruvate and NADH + H+ from glycolysis, the pathway of glycolysis as it is known today took almost 100 years to fully discover. The combined results of many experiments were required in order to understand the pathway as a whole
23.
Gibbs free energy
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Just as in mechanics, where the decrease in potential energy is defined as maximum useful work that can be performed, similarly different potentials have different meanings. The Gibbs energy is also the potential that is minimized when a system reaches chemical equilibrium at constant pressure and temperature. Its derivative with respect to the coordinate of the system vanishes at the equilibrium point. As such, a reduction in G is a condition for the spontaneity of processes at constant pressure and temperature. The Gibbs free energy, originally called available energy, was developed in the 1870s by the American scientist Josiah Willard Gibbs. The initial state of the body, according to Gibbs, is supposed to be such that the body can be made to pass from it to states of dissipated energy by reversible processes. In his 1876 magnum opus On the Equilibrium of Heterogeneous Substances, according to the second law of thermodynamics, for systems reacting at STP, there is a general natural tendency to achieve a minimum of the Gibbs free energy. A quantitative measure of the favorability of a reaction at constant temperature and pressure is the change ΔG in Gibbs free energy that is caused by the reaction. As a necessary condition for the reaction to occur at constant temperature and pressure, ΔG must be smaller than the non-PV work, ΔG equals the maximum amount of non-PV work that can be performed as a result of the chemical reaction for the case of reversible process. The equation can be seen from the perspective of the system taken together with its surroundings. First assume that the reaction at constant temperature and pressure is the only one that is occurring. Then the entropy released or absorbed by the system equals the entropy that the environment must absorb or release, the reaction will only be allowed if the total entropy change of the universe is zero or positive. This is reflected in a negative ΔG, and the reaction is called exergonic, if we couple reactions, then an otherwise endergonic chemical reaction can be made to happen. In traditional use, the term free was included in Gibbs free energy to mean available in the form of useful work, the characterization becomes more precise if we add the qualification that it is the energy available for non-volume work. However, a number of books and journal articles do not include the attachment free. This is the result of a 1988 IUPAC meeting to set unified terminologies for the scientific community. This standard, however, has not yet been universally adopted. Further, Gibbs stated, In this description, as used by Gibbs, ε refers to the energy of the body, η refers to the entropy of the body
24.
Skeletal muscle
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Skeletal muscle is one of three major muscle types, the others being cardiac muscle and smooth muscle. It is a form of striated muscle tissue which is under the control of the somatic nervous system. Most skeletal muscles are attached to bones by bundles of collagen fibers known as tendons, a skeletal muscle refers to multiple bundles of cells called muscle fibers. The fibres and muscles are surrounded by connective tissue layers called fasciae, Muscle fibres, or muscle cells, are formed from the fusion of developmental myoblasts in a process known as myogenesis. Muscle fibres are cylindrical, and have more than one nucleus, Muscle fibers are in turn composed of myofibrils. The myofibrils are composed of actin and myosin filaments, repeated in units called sarcomeres, the sarcomere is responsible for the striated appearance of skeletal muscle, and forms the basic machinery necessary for muscle contraction. Connective tissue is present in all muscles as fascia, Muscle fibres are the individual contractile units within muscle. A single muscle such as the biceps contains many muscle fibres, another group of cells, the myosatellite cells are found between the basement membrane and the sarcolemma of muscle fibers. These cells are normally quiescent but can be activated by exercise or pathology to provide additional myonuclei for muscle growth or repair, development Individual muscle fibers are formed during development from the fusion of several undifferentiated immature cells known as myoblasts into long, cylindrical, multi-nucleated cells. Differentiation into this state is completed before birth with the cells continuing to grow in size thereafter. Microanatomy Skeletal muscle exhibits a distinctive banding pattern when viewed under the due to the arrangement of cytoskeletal elements in the cytoplasm of the muscle fibers. The principal cytoplasmic proteins are myosin and actin which are arranged in a unit called a sarcomere. The interaction of myosin and actin is responsible for muscle contraction, every single organelle and macromolecule of a muscle fiber is arranged to ensure form meets function. The cell membrane is called the sarcolemma with the known as the sarcoplasm. In the sarcoplasm are the myofibrils, the myofibrils are long protein bundles about 1 micrometer in diameter each containing myofilaments. Pressed against the inside of the sarcolemma are the unusual flattened myonuclei, between the myofibrils are the mitochondria. While the muscle fiber does not have a smooth endoplasmic reticulum, the sarcoplasmic reticulum surrounds the myofibrils and holds a reserve of the calcium ions needed to cause a muscle contraction. Periodically, it has dilated end sacs known as terminal cisternae and these cross the muscle fiber from one side to the other
25.
Adipocyte
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Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. There are two types of tissue, white adipose tissue and brown adipose tissue, which are also known as white fat and brown fat, respectively. Most recently, the presence of beige adipocytes with an expression pattern distinct from either white or brown adipocytes has been described. White fat cells or monovacuolar cells contain a lipid droplet surrounded by a layer of cytoplasm. The nucleus is flattened and located on the periphery, a typical fat cell is 0.1 mm in diameter with some being twice that size and others half that size. The fat stored is in a state, and is composed primarily of triglycerides. White fat cells secrete many proteins acting as such as resistin, adiponectin, leptin and apelin. An average human adult has 30 billion fat cells with a weight of 30 lbs or 13.5 kg, if excess weight is gained as an adult, fat cells increase in size about fourfold before dividing and increasing the absolute number of fat cells present. Brown fat cells or plurivacuolar cells are polygonal in shape, unlike white fat cells, these cells have considerable cytoplasm, with lipid droplets scattered throughout. The nucleus is round, and, although eccentrically located, it is not in the periphery of the cell, the brown color comes from the large quantity of mitochondria. Brown fat, also known as fat, is used to generate heat. Pre-adipocytes are undifferentiated fibroblasts that can be stimulated to form adipocytes, recent studies shed light into potential molecular mechanisms in the fate determination of pre-adipocytes although the exact lineage of adipocyte is still unclear. The variation of body fat distribution resulting from normal growth is influenced by nutritional and hormonal status in dependence on intrinsic differences in cells found in each adipose depot, mesenchymal stem cells can differentiate into adipocytes, connective tissue, muscle or bone. The term lipoblast is used to describe the precursor of the adult cell, the term lipoblastoma is used to describe a tumor of this cell type. Even after marked weight loss, the body never loses adipocytes. As a rule, to changes in weight. However, if the adipocytes in the body reach their capacity of fat. Adult rats of various strains became obese when they were fed a highly palatable diet for several months, analysis of their adipose tissue morphology revealed increases in both adipocyte size and number in most depots. Reintroduction of an ordinary chow diet to such animals precipitated a period of loss during which only mean adipocyte size returned to normal
26.
Mechanistic target of rapamycin
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The mechanistic target of rapamycin, also known as FK506-binding protein 12-rapamycin-associated protein 1, is a kinase that in humans is encoded by the MTOR gene. MTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases, MTOR links with other proteins and serves as a core component of two distinct protein complexes, mTOR complex 1 and mTOR complex 2, which regulate different cellular processes. As a core component of mTORC2, mTOR also functions as a protein kinase that promotes the activation of insulin receptors. MTORC2 has also implicated in the control and maintenance of the actin cytoskeleton. MTOR was first named as the target of rapamycin. Rapamycin was discovered in a sample from Easter Island, known locally as Rapa Nui. The bacterium Streptomyces hygroscopicus, isolated from that sample, produces an antifungal that researchers named rapamycin after the island, rapamycin arrests fungal activity at the G1 phase of the cell cycle. In mammals, it suppresses the immune system by blocking the G1 to S phase transition in T-lymphocytes, thus, it is used as an immunosuppressant following organ transplantation. They isolated rapamycin-resistant mutants of Saccharomyces cerevisiae and discovered that mutations in any of three genes can confer rapamycin resistance. Two of the genes were named TOR1 and TOR2 for targets of rapamycin and in honor of the Spalentor, the third gene is FPR1, which encodes the yeast ortholog of FKBP12 binding protein in the TOR complexes. Loss of function mutations in FPR1 confer resistance to rapamycin, and also to FK506, several groups also described the protein independently in the year 1994 using names such as FRAP, RAFT1, RAPT1 and SEP to refer to the protein. Due to the ubiquity of mTOR in animals the meaning of the m has been changed from mammalian to mechanistic. MTOR integrates the input from upstream pathways, including insulin, growth factors, MTOR also senses cellular nutrient, oxygen, and energy levels. Rapamycin inhibits mTOR by associating with its intracellular receptor FKBP12, the FKBP12-rapamycin complex binds directly to the FKBP12-Rapamycin Binding domain of mTOR, inhibiting its activity. MTOR is the subunit of two structurally distinct complexes, mTORC1 and mTORC2. Both complexes localize to different subcellular compartments, thus affecting their activation and function, MTOR Complex 1 is composed of MTOR, regulatory-associated protein of MTOR, mammalian lethal with SEC13 protein 8 and the non-core components PRAS40 and DEPTOR. This complex functions as a sensor and controls protein synthesis. The activity of mTORC1 is regulated by rapamycin, insulin, growth factors, phosphatidic acid, certain amino acids and their derivatives, mechanical stimuli, MTOR Complex 2 is composed of MTOR, rapamycin-insensitive companion of MTOR, MLST8, and mammalian stress-activated protein kinase interacting protein 1
27.
Prokaryote
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A prokaryote is a unicellular organism that lacks a membrane-bound nucleus, mitochondria, or any other membrane-bound organelle. The word prokaryote comes from the Greek πρό before and καρυόν nut or kernel, prokaryotes can be divided into two domains, Archaea and bacteria. In contrast, species with nuclei and organelles are placed in the domain Eukaryota, in the prokaryotes, all the intracellular water-soluble components are located together in the cytoplasm enclosed by the cell membrane, rather than in separate cellular compartments. Bacteria, however, do possess protein-based bacterial microcompartments, which are thought to act as primitive organelles enclosed in protein shells, some prokaryotes, such as cyanobacteria may form large colonies. Others, such as myxobacteria, have multicellular stages in their life cycles, molecular studies have provided insight into the evolution and interrelationships of the three domains of biological species. Eukaryotes are organisms, including humans, whose cells have a well defined membrane-bound nucleus, the division between prokaryotes and eukaryotes reflects the existence of two very different levels of cellular organization. Distinctive types of prokaryotes include extremophiles and methanogens, these are common in extreme environments. Prokaryotes have a cytoskeleton, albeit more primitive than that of the eukaryotes. At least some also contain intracellular structures that can be seen as primitive organelles. Membranous organelles are known in some groups of prokaryotes, such as vacuoles or membrane systems devoted to special metabolic properties, in addition, some species also contain carbohydrate-enclosed microcompartments, which have distinct physiological roles. Most prokaryotes are between 1 µm and 10 µm, but they can vary in size from 0.2 µm to 750 µm, Bacteria and archaea reproduce through asexual reproduction, usually by binary fission. DNA transfer between prokaryotic cells occurs in bacteria and archaea, although it has mainly studied in bacteria. In bacteria, gene transfer occurs by three processes and these are bacterial virus -mediated transduction, plasmid-mediated conjugation, and natural transformation. Transduction of bacterial genes by bacteriophage appears to reflect an occasional error during intracellular assembly of virus particles, the transfer of bacterial DNA is under the control of the bacteriophage’s genes rather than bacterial genes. Conjugation in the well-studied E. coli system is controlled by plasmid genes, infrequently during this process, a plasmid may integrate into the host bacterial chromosome, and subsequently transfer part of the host bacterial DNA to another bacterium. Plasmid mediated transfer of host bacterial DNA also appears to be a process rather than a bacterial adaptation. Natural bacterial transformation involves the transfer of DNA from one bacterium to another through the intervening medium, for a bacterium to bind, take up and recombine donor DNA into its own chromosome, it must first enter a special physiological state called competence. About 40 genes are required in Bacillus subtilis for the development of competence, the length of DNA transferred during B. subtilis transformation can be as much as a third to the whole chromosome
28.
Protein kinase
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A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them. Phosphorylation usually results in a change of the target protein by changing enzyme activity, cellular location. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes, up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction. The chemical activity of a kinase involves transferring a phosphate group from a nucleoside triphosphate, most kinases act on both serine and threonine, others act on tyrosine, and a number act on all three. There are also protein kinases that phosphorylate other amino acids, including histidine kinases that phosphorylate histidine residues, because protein kinases have profound effects on a cell, their activity is highly regulated. Kinases are turned on or off by phosphorylation, by binding of proteins or inhibitor proteins, or small molecules. The catalytic subunits of protein kinases are highly conserved. Eukaryotic protein kinases are enzymes that belong to an extensive family of proteins that share a conserved catalytic core. There are a number of conserved regions in the domain of protein kinases. In the N-terminal extremity of the catalytic domain there is a stretch of residues in the vicinity of a lysine amino acid. In the central part of the domain, there is a conserved aspartic acid. The human protein kinase family is divided into the groups, AGC kinases - containing PKA, PKC. CaM kinases - containing the calcium/calmodulin-dependent protein kinases, cK1 - containing the casein kinase 1 group. CMGC - containing CDK, MAPK, GSK3 and CLK kinases, STE - containing the homologs of yeast Sterile 7, Sterile 11, and Sterile 20 kinases. TK - containing the tyrosine kinases, TKL - containing the tyrosine-kinase like group of kinases. Serine/threonine protein kinases phosphorylate the OH group of serine or threonine, activity of these protein kinases can be regulated by specific events, as well as numerous chemical signals, including cAMP/cGMP, diacylglycerol, and Ca2+/calmodulin. One very important group of protein kinases are the MAP kinases, important subgroups are the kinases of the ERK subfamily, typically activated by mitogenic signals, and the stress-activated protein kinases JNK and p38. While MAP kinases are serine/threonine-specific, they are activated by combined phosphorylation on serine/threonine and tyrosine residues, tyrosine-specific protein kinases phosphorylate tyrosine amino acid residues, and like serine/threonine-specific kinases are used in signal transduction
29.
Receptor (biochemistry)
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In biochemistry and pharmacology, a receptor is a protein molecule that receives chemical signals from outside a cell. When such chemical signals bind to a receptor, they cause some form of cellular/tissue response, however, sometimes in pharmacology, the term is also used to include other proteins that are drug targets, such as enzymes, transporters and ion channels. Receptor proteins can be classified by their location, transmembrane receptors include ion channel-linked receptors, G protein-linked hormone receptors, and enzyme-linked hormone receptors. Intracellular receptors are found inside the cell, and include cytoplasmic receptors. The endogenously designated -molecule for a receptor is referred to as its endogenous ligand. E. g. the endogenous ligand for the acetylcholine receptor is acetylcholine but the receptor can also be activated by nicotine. Each receptor is linked to a specific cellular biochemical pathway, while numerous receptors are found in most cells, each receptor will only bind with ligands of a particular structure, much like how locks will only accept specifically shaped keys. When a ligand binds to its receptor, it activates or inhibits the receptors associated biochemical pathway. The ligand-binding cavities are located at the interface between the subunits, type 2, G protein-coupled receptors – This is the largest family of receptors and includes the receptors for several hormones and slow transmitters e. g. dopamine, metabotropic glutamate. They are composed of seven transmembrane alpha helices, the loops connecting the alpha helices form extracellular and intracellular domains. The aforementioned receptors are coupled to different intracellular effector systems via G proteins, the insulin receptor is an example. Type 4, Nuclear receptors – While they are called nuclear receptors, they are located in the cytoplasm. They are composed of a C-terminal ligand-binding region, a core DNA-binding domain, the core region has two zinc fingers that are responsible for recognizing the DNA sequences specific to this receptor. The N terminus interacts with other transcription factors in a ligand-independent manner. Steroid and thyroid-hormone receptors are examples of such receptors, membrane receptors may be isolated from cell membranes by complex extraction procedures using solvents, detergents, and/or affinity purification. The structures and actions of receptors may be studied by using methods such as X-ray crystallography, NMR, circular dichroism. Computer simulations of the behavior of receptors have been used to gain understanding of their mechanisms of action. Ligand binding is an equilibrium process, ligands bind to receptors and dissociate from them according to the law of mass action
30.
Protein dynamics
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Proteins are generally thought to adopt unique structures determined by their amino acid sequences, as outlined by Anfinsens dogma. However, proteins are not strictly static objects, but rather populate ensembles of conformations, transitions between these states occur on a variety of length scales and time scales, and have been linked to functionally relevant phenomena such as allosteric signaling and enzyme catalysis. The study of dynamics is most directly concerned with the transitions between these states, but can also involve the nature and equilibrium populations of the states themselves. Portions of protein structures often deviate from the equilibrium state, some such excursions are harmonic, such as stochastic fluctuations of chemical bonds and bond angles. Others are anharmonic, such as sidechains that jump between separate discrete energy minima, or rotamers, evidence for local flexibility is often obtained from NMR spectroscopy. Flexible and potentially disordered regions of a protein can be detected using the random coil index, flexibility in folded proteins can be identified by analyzing the spin relaxation of individual atoms in the protein. Many residues are in spatial proximity in protein structures. This is true for most residues that are contiguous in the primary sequence, because of this proximity, these residuess energy landscapes become coupled based on various biophysical phenomena such as hydrogen bonds, ionic bonds, and van der Waals interactions. Transitions between states for such sets of residues therefore become correlated and this is perhaps most obvious for surface-exposed loops, which often shift collectively to adopt different conformations in different crystal structures. However, coupled conformational heterogeneity is also evident in secondary structure. For example, consecutive residues and residues offset by 4 in the sequence often interact in α helices. When these coupled residues form pathways linking functionally important parts of a protein, the presence of multiple domains in proteins gives rise to a great deal of flexibility and mobility, leading to protein domain dynamics. Domain motions can be inferred by comparing different structures of a protein and they can also be suggested by sampling in extensive molecular dynamics trajectories and principal component analysis. The phosphoinositide domain swivels between two states in order to bring a group from the active site of the nucleotide binding domain to that of the phosphoenolpyruvate/pyruvate domain. The phosphate group is moved over a distance of 45 Å involving a domain motion of about 100 degrees around a single residue. In enzymes, the closure of one domain onto another captures a substrate by an induced fit, a detailed analysis by Gerstein led to the classification of two basic types of domain motion, hinge and shear. Only a relatively small portion of the chain, namely the inter-domain linker, a study by Hayward found that the termini of α-helices and β-sheets form hinges in a large number of cases. Many hinges were found to two secondary structure elements acting like hinges of a door, allowing an opening and closing motion to occur
31.
Allostery
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In biochemistry, allosteric regulation is the regulation of an enzyme by binding an effector molecule at a site other than the enzymes active site. The site to which the effector binds is termed the allosteric site, Allosteric sites allow effectors to bind to the protein, often resulting in a conformational change involving protein dynamics. Effectors that enhance the activity are referred to as allosteric activators. Allosteric regulations are an example of control loops, such as feedback from downstream products or feedforward from upstream substrates. Long-range allostery is especially important in cell signaling, Allosteric regulation is also particularly important in the cells ability to adjust enzyme activity. The term allostery comes from the Greek allos, other, and stereos and this is in reference to the fact that the regulatory site of an allosteric protein is physically distinct from its active site. Most allosteric effects can be explained by the concerted MWC model put forth by Monod, Wyman, and Changeux, or by the model described by Koshland, Nemethy. Both postulate that enzyme subunits exist in one of two conformations, tensed or relaxed, and that relaxed subunits bind substrate more readily than those in the tense state, the two models differ most in their assumptions about subunit interaction and the preexistence of both states. Thus, all subunits must exist in the same conformation, the model further holds that, in the absence of any ligand, the equilibrium favors one of the conformational states, T or R. The equilibrium can be shifted to the R or T state through the binding of one ligand to a site that is different from the active site. The sequential model of allosteric regulation holds that subunits are not connected in such a way that a change in one induces a similar change in the others. Thus, all enzyme subunits do not necessitate the same conformation, moreover, the sequential model dictates that molecules of a substrate bind via an induced fit protocol. In general, when a subunit randomly collides with a molecule of substrate, while such an induced fit converts a subunit from the tensed state to relaxed state, it does not propagate the conformational change to adjacent subunits. Instead, substrate-binding at one subunit only slightly alters the structure of other subunits so that their sites are more receptive to substrate. A morpheein is a structure that can exist as an ensemble of physiologically significant. Transitions between alternate morpheein assemblies involve oligomer dissociation, conformational change in the state, and reassembly to a different oligomer. The required oligomer disassembly step differentiates the morpheein model for allosteric regulation from the classic MWC, porphobilinogen synthase is the prototype morpheein. Ensemble models like the Ensemble Allosteric Model and Allosteric Ising Model assume that each domain of the system can adopt two states similar to the MWC model, molecular dynamics simulations can be used to estimate a systemss statistical ensemble so that it can be analyzed with the allostery landscape model
32.
TP53
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This homolog is crucial in multicellular organisms, where it prevents cancer formation, thus, functions as a tumor suppressor. As such, p53 has been described as the guardian of the genome because of its role in conserving stability by preventing genome mutation, hence TP53 is classified as a tumor suppressor gene. The name p53 was given in 1979 describing the apparent molecular mass, however, the actual mass of the full-length p53 protein based on the sum of masses of the amino acid residues is only 43.7 kDa. This difference is due to the number of proline residues in the protein. In addition to the protein, the human TP53 gene encodes at least 15 protein isoforms. All these p53 proteins are called the p53 isoforms, the TP53 gene is the most frequently mutated gene in human cancer, indicating that the TP53 gene plays a crucial role in preventing cancer formation. TP53 gene encodes proteins that bind to DNA and regulate gene expression to prevent mutations of the genome, in humans, the TP53 gene is located on the short arm of chromosome 17. The gene spans 20 kb, with a non-coding exon 1, TP53 orthologs have been identified in most mammals for which complete genome data are available. In humans, a common polymorphism involves the substitution of an arginine for a proline at codon position 72, many studies have investigated a genetic link between this variation and cancer susceptibility, however, the results have been controversial. For instance, a meta-analysis from 2009 failed to show a link for cervical cancer, a 2011 study found that the TP53 proline mutation did have a profound effect on pancreatic cancer risk among males. A study of Arab women found that proline homozygosity at TP53 codon 72 is associated with a risk for breast cancer. A2011 study found that TP53 codon 72 polymorphism was associated with a risk of lung cancer. Meta-analyses from 2011 found no significant associations between TP53 codon 72 polymorphisms and both colorectal cancer risk and endometrial cancer risk, a 2011 study of a Brazilian birth cohort found an association between the non mutant arginine TP53 and individuals without a family history of cancer. Another 2011 study found that the p53 homozygous genotype was associated with an increased risk for renal cell carcinoma. An acidic N-terminus transcription-activation domain, also known as activation domain 1, activation domain 2 important for apoptotic activity, residues 43-63. Proline rich domain important for the activity of p53 by nuclear exportation via MAPK. Contains one zinc atom and several arginine amino acids, residues 102-292 and this region is responsible for binding the p53 co-repressor LMO3. Nuclear localization signaling domain, residues 316-325, tetramerization is essential for the activity of p53 in vivo
33.
Signal transduction
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Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding in a receptor give rise to a cascade of events along a signalling pathway. When signalling pathways interact with one another they form networks, which allow cellular responses to be coordinated and these molecular events are the basic mechanisms controlling cell growth, proliferation, metabolism and many other processes. In multicellular organisms, signal transduction pathways have evolved to regulate cell communication in a variety of ways. Each component of a pathway is classified according to the role it plays with respect to the initial stimulus. Ligands are termed first messengers, while receptors are the signal transducers, such effectors are often linked to second messengers, which can activate secondary effectors, and so on. Depending on the efficiency of the nodes, a signal can be amplified, as with other signals, the transduction of biological signals is characterised by delay, noise and interference, which can range from negligible to pathological. With the advent of computational biology, the analysis of signalling pathways and networks has become a tool to understand cellular functions. The basis for signal transduction is the transformation of a certain stimulus into a biochemical signal, traditionally, signals that reach the central nervous system are classified as senses. These are transmitted from neuron to neuron in a process called synaptic transmission, many other intercellular signal relay mechanisms exist in multicellular organisms, such as those that govern embryonic development. The majority of signal transduction pathways involve the binding of signalling molecules, known as ligands, the combination of a signaling molecule with a receptor causes a change in the conformation of the receptor, known as receptor activation. Most ligands are soluble molecules from the medium which bind to cell surface receptors. These include growth factors, cytokines and neurotransmitters, components of the extracellular matrix such as fibronectin and hyaluronan can also bind to such receptors. In addition, some such as steroid hormones are lipid-soluble. In the case of hormone receptors, their stimulation leads to binding to the promoter region of steroid-responsive genes. Not all classifications of signalling molecules take into account the nature of each class member. For example, odorants belong to a range of molecular classes, as do neurotransmitters. Moreover, some molecules may fit more than one class, e. g. epinephrine is a neurotransmitter when secreted by the central nervous system
34.
Na+/K+-ATPase
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Na+/K+-ATPase is an enzyme found in the plasma membrane of all animal cells. The Na+/K+-ATPase enzyme is a pump that pumps sodium out of cells while pumping potassium into cells. This pumping is active and is important for cell physiology, an example application is nerve conduction. Active transport is responsible for the fact that cells contain a high concentration of potassium ions. The mechanism responsible for this is the pump, which moves these two ions in opposite directions across the plasma membrane. This was investigated by following the passage of radioactively labeled ions across the membrane of certain cells. It was found that the concentrations of sodium and potassium ions on the two sides of the membrane are interdependent, suggesting that the same carrier transports both ions. It is now known that the carrier is an ATP-ase and that it pumps three sodium ions out of the cell for every two potassium ions pumped in. The sodium-potassium pump was discovered in the 1950s by a Danish scientist, Jens Christian Skou, the Na+/K+-ATPase helps maintain resting potential, effect transport, and regulate cellular volume. It also functions as a signal transducer/integrator to regulate MAPK pathway, ROS, in most animal cells, the Na+/K+-ATPase is responsible for about 1/5 of the cells energy expenditure. For neurons, the Na+/K+-ATPase can be responsible for up to 2/3 of the energy expenditure. In order to maintain the membrane potential, cells keep a low concentration of sodium ions. The sodium-potassium pump mechanism moves 3 sodium ions out and moves 2 potassium ions in, thus, in total, the action of the sodium-potassium pump is not the only mechanism responsible for the generation of the resting membrane potential. Also, the permeability of the cells plasma membrane for the different ions plays an important role. All mechanisms involved are explained in the article on generation of the resting membrane potential. Another important task of the Na+-K+ pump is to provide a Na+ gradient that is used by certain carrier processes, similar processes are located in the renal tubular system. Failure of the Na+-K+ pumps can result in swelling of the cell, a cells osmolarity is the sum of the concentrations of the various ion species and many proteins and other organic compounds inside the cell. When this is higher than the osmolarity outside of the cell and this can cause the cell to swell up and lyse
35.
Osmoregulation
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Osmotic pressure is a measure of the tendency of water to move into one solution from another by osmosis. The higher the pressure of a solution, the more water tends to move into it. Pressure must be exerted on the side of a selectively permeable membrane to prevent diffusion of water by osmosis from the side containing pure water. Two major types of osmoregulation are osmoconformers and osmoregulators, osmoconformers match their body osmolarity to their environment actively or passively. Most marine invertebrates are osmoconformers, although their ionic composition may be different from that of seawater, osmoregulators tightly regulate their body osmolarity, maintaining constant internal conditions. They are more common in the animal kingdom, osmoregulators actively control salt concentrations despite the salt concentrations in the environment. The gills actively uptake salt from the environment by the use of mitochondria-rich cells, water will diffuse into the fish, so it excretes a very hypotonic urine to expel all the excess water. A marine fish has an internal osmotic concentration lower than that of the seawater, so it tends to lose water. It actively excretes salt out from the gills, most fish are stenohaline, which means they are restricted to either salt or fresh water and cannot survive in water with a different salt concentration than they are adapted to. However, some show a tremendous ability to effectively osmoregulate across a broad range of salinities, fish with this ability are known as euryhaline species. Flounder have been observed to inhabit two utterly disparate environments — marine and fresh water — and it is inherent to adapt to both by bringing in behavioral and physiological modifications. Some marine fish, like sharks, have adopted a different, efficient mechanism to conserve water and they retain urea in their blood in relatively higher concentration. Urea damages living tissues so, to cope with this problem and this provides a better solution to ureas toxicity. Sharks, having slightly higher concentration, do not drink water like fresh water fish. Strong winds, low humidity and high temperatures all increase evapotranspiration from leaves, abscisic acid is an important hormone in helping plants to conserve water — it causes stomata to close and stimulates root growth so that more water can be absorbed. Plants share with animals the problems of obtaining water but, unlike in animals, certain plants have evolved methods of water conservation. Xerophytes are plants that can survive in dry habitats, such as deserts, succulent plants such as the cacti store water in the vacuoles of large parenchyma tissues. Other plants have modifications to reduce water loss, such as needle-shaped leaves, sunken stomata
36.
Homeostasis
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Each of these variables is controlled by a separate “homeostat”, which, together, maintain life. The concept was described by French physiologist Claude Bernard in 1865, the term cybernetics is applied to technological control systems such as thermostats, which function as homeostats, but is often defined much more broadly than the biological term homeostasis. The word homeostasis uses combining forms of homeo- and -stasis, New Latin from Greek, ὅμοιος homoios, similar and στάσις stasis, standing still, yielding the idea of staying the same. The conceptual origins of homeostasis reach back to the ancient Greek concepts of balance, harmony, equilibrium, following these hypotheses, Hippocrates compared health to the harmonious balance of the elements, and illness and disease to the systematic disharmony of these elements. Cannon published an extrapolation from Bernards 1865 work naming his theory homeostasis, Cannon further posited that threats to homeostasis might originate from the external environment or the internal environment, and could be physical or psychological, as in emotional distress. Cannon identified these negative feedback systems and emphasized that, regardless of the nature of the threat to homeostasis, the metabolic processes of all living organisms can only take place in very specific physical and chemical environments. The conditions vary with each organism, and with whether the chemical processes take place inside the cell or in the bathing the cells in multicellular creatures. However, a great many other homeostats, encompassing many aspects of human physiology, if an entity is homeostatically controlled it does not imply that its value is necessarily absolutely steady in health. Core body temperature is, for instance, regulated by a homeostat with temperature sensors in, amongst others, however the set point of the regulator is regularly reset. For instance, core temperature in humans varies during the course of the day, with the lowest temperatures occurring at night. The temperature regulators set point is readjusted in adult women at the start of the phase of the menstrual cycle. The temperature regulators set point is reset during infections to produce a fever, Homeostasis does not govern every activity in the body. For instance the signal from the sensor to the effector is, of necessity, highly variable in order to information about the direction. Similarly the effector’s response needs to be adjustable to reverse the error – in fact it should be very nearly in proportion to the error that is threatening the internal environment. The sensors send messages via sensory nerves to the medulla oblongata of the brain indicating whether the pressure has fallen or risen. One of the effector organs is the heart rate is stimulated to rise when the arterial blood pressure falls. Thus the heart rate is not homeostatically controlled, but is one of effector responses to errors in the blood pressure. Another example is the rate of sweating, the blood urea concentration is an example
37.
Enzyme inhibitor
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An enzyme inhibitor is a molecule that binds to an enzyme and decreases its activity. Since blocking an enzymes activity can kill a pathogen or correct a metabolic imbalance and they are also used in pesticides. The binding of an inhibitor can stop a substrate from entering the active site and/or hinder the enzyme from catalyzing its reaction. Inhibitor binding is reversible or irreversible. Irreversible inhibitors usually react with the enzyme and change it chemically and these inhibitors modify key amino acid residues needed for enzymatic activity. In contrast, reversible inhibitors bind non-covalently and different types of inhibition are produced depending on whether these inhibitors bind to the enzyme, many drug molecules are enzyme inhibitors, so their discovery and improvement is an active area of research in biochemistry and pharmacology. A medicinal enzyme inhibitor is often judged by its specificity and its potency, a high specificity and potency ensure that a drug will have few side effects and thus low toxicity. Enzyme inhibitors also occur naturally and are involved in the regulation of metabolism, for example, enzymes in a metabolic pathway can be inhibited by downstream products. This type of negative feedback slows the production line when products begin to build up and is an important way to maintain homeostasis in a cell, other cellular enzyme inhibitors are proteins that specifically bind to and inhibit an enzyme target. This can help control enzymes that may be damaging to a cell, a well-characterised example of this is the ribonuclease inhibitor, which binds to ribonucleases in one of the tightest known protein–protein interactions. Natural enzyme inhibitors can also be poisons and are used as defences against predators or as ways of killing prey, reversible inhibitors attach to enzymes with non-covalent interactions such as hydrogen bonds, hydrophobic interactions and ionic bonds. Multiple weak bonds between the inhibitor and the active site combine to produce strong and specific binding, in contrast to substrates and irreversible inhibitors, reversible inhibitors generally do not undergo chemical reactions when bound to the enzyme and can be easily removed by dilution or dialysis. There are four kinds of reversible enzyme inhibitors and they are classified according to the effect of varying the concentration of the enzymes substrate on the inhibitor. In competitive inhibition, the substrate and inhibitor cannot bind to the enzyme at the same time, as shown in the figure on the right. This usually results from the inhibitor having an affinity for the site of an enzyme where the substrate also binds. This type of inhibition can be overcome by high concentrations of substrate. However, the apparent Km will increase as it takes a higher concentration of the substrate to reach the Km point, competitive inhibitors are often similar in structure to the real substrate. In uncompetitive inhibition, the inhibitor binds only to the substrate-enzyme complex and this type of inhibition causes Vmax to decrease and Km to decrease
38.
GSK-3
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Glycogen synthase kinase 3 is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. First discovered in 1980 as a kinase for its namesake, Glycogen synthase. In mammals GSK-3 is encoded by two genes, GSK-3 alpha and GSK-3 beta. GSK-3 functions by phosphorylating a serine or threonine residue on its target substrate, a positively charged pocket adjacent to the active site binds a priming phosphate group attached to a serine or threonine four residues C-terminal of the target phosphorylation site. The active site, at residues 181,200,97, phosphorylation of a protein by GSK-3 usually inhibits the activity of its downstream target. GSK-3 is active in a number of intracellular signaling pathways, including cellular proliferation, migration, glucose regulation. GSK-3 was originally discovered in the context of its involvement in regulating glycogen synthase, after being primed by casein kinase 2, glycogen synthase gets phosphorylated at a cluster of three C-terminal serine residues, reducing its activity. However, these interactions have not been confirmed, as these pathways can be inhibited without the up-regulation of GSK-3, GSK-3 has also been shown to regulate immune and migratory processes. GSK-3 participates in a number of signaling pathways in the immune response, including pro-inflammatory cytokine. The inactivation of GSK3B by various protein kinases also affects the immune response by inducing cytokine production and proliferation in naïve. GSK-3 is also tied to pathways of cell proliferation and apoptosis. GSK-3 has been shown to phosphorylate Beta-catenin, thus targeting it for degradation, GSK-3 is therefore a part of the canonical Beta-catenin/Wnt pathway, which signals the cell to divide and proliferate. GSK-3 also participates in a number of signaling pathways by phosphorylating transcription factors that regulate apoptosis. GSK-3 can promote apoptosis by both activating pro-apoptotic factors such as p53 and inactivating survival-promoting factors through phosphorylation, overall, GSK-3 appears to both promote and inhibit apoptosis, and this regulation varies depending on the specific molecular and cellular context. Due to its importance across numerous cellular functions, GSK-3 activity is subject to tight regulation, the speed and efficacy of GSK-3 phosphorylation is regulated by a number of factors. Phosphorylation of certain GSK-3 residues can increase or decrease its ability to bind substrate, further, GSK-3 is unusual among kinases in that it usually requires a priming kinase to first phosphorylate a substrate. Depending on the pathway in which it is being utilized, GSK-3 may be regulated by cellular localization or the formation of protein complexes. Due to its involvement in a number of signaling pathways
. PMID 28250014.
