1.
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
2.
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
3.
DNA
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Deoxyribonucleic acid is a molecule that carries the genetic instructions used in the growth, development, functioning and reproduction of all known living organisms and many viruses. DNA and RNA are nucleic acids, alongside proteins, lipids and complex carbohydrates, most DNA molecules consist of two biopolymer strands coiled around each other to form a double helix. The two DNA strands are termed polynucleotides since they are composed of simpler units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases—cytosine, guanine, adenine, or thymine —a sugar called deoxyribose, and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two polynucleotide strands are bound together, according to base pairing rules, with hydrogen bonds to make double-stranded DNA. The total amount of related DNA base pairs on Earth is estimated at 5.0 x 1037, in comparison the total mass of the biosphere has been estimated to be as much as 4 trillion tons of carbon. The DNA backbone is resistant to cleavage, and both strands of the double-stranded structure store the same biological information and this information is replicated as and when the two strands separate. A large part of DNA is non-coding, meaning that these sections do not serve as patterns for protein sequences, the two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases and it is the sequence of these four nucleobases along the backbone that encodes biological information. RNA strands are created using DNA strands as a template in a process called transcription, under the genetic code, these RNA strands are translated to specify the sequence of amino acids within proteins in a process called translation. Within eukaryotic cells DNA is organized into structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, eukaryotic organisms store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts. In contrast prokaryotes store their DNA only in the cytoplasm, within the eukaryotic chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed, DNA was first isolated by Friedrich Miescher in 1869. DNA is used by researchers as a tool to explore physical laws and theories, such as the ergodic theorem. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro-, among notable advances in this field are DNA origami and DNA-based hybrid materials. DNA is a polymer made from repeating units called nucleotides
4.
RNA
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Ribonucleic acid is a polymeric molecule essential in various biological roles in coding, decoding, regulation, and expression of genes. RNA and DNA are nucleic acids, and, along with proteins and carbohydrates, like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA it is more often found in nature as a single-strand folded onto itself, rather than a paired double-strand. Cellular organisms use messenger RNA to convey information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome, some RNA molecules play an active role within cells by catalyzing biological reactions, controlling gene expression, or sensing and communicating responses to cellular signals. One of these processes is protein synthesis, a universal function where RNA molecules direct the assembly of proteins on ribosomes. This process uses transfer RNA molecules to deliver amino acids to the ribosome, analysis of these RNAs has revealed that they are highly structured. Unlike DNA, their structures do not consist of long double helices, in this fashion, RNAs can achieve chemical catalysis. For instance, determination of the structure of the enzyme that catalyzes peptide bond formation—revealed that its active site is composed entirely of RNA. Each nucleotide in RNA contains a sugar, with carbons numbered 1 through 5. A base is attached to the 1 position, in general, adenine, cytosine, guanine, adenine and guanine are purines, cytosine and uracil are pyrimidines. A phosphate group is attached to the 3 position of one ribose, the phosphate groups have a negative charge each, making RNA a charged molecule. The bases form hydrogen bonds between cytosine and guanine, between adenine and uracil and between guanine and uracil, however, other interactions are possible, such as a group of adenine bases binding to each other in a bulge, or the GNRA tetraloop that has a guanine–adenine base-pair. An important structural feature of RNA that distinguishes it from DNA is the presence of a group at the 2 position of the ribose sugar. The A-form geometry results in a deep and narrow major groove. RNA is transcribed with only four bases, but these bases, pseudouridine, in which the linkage between uracil and ribose is changed from a C–N bond to a C–C bond, and ribothymidine are found in various places. Another notable modified base is hypoxanthine, a deaminated adenine base whose nucleoside is called inosine, inosine plays a key role in the wobble hypothesis of the genetic code. The specific roles of many of these modifications in RNA are not fully understood, the functional form of single-stranded RNA molecules, just like proteins, frequently requires a specific tertiary structure. The scaffold for this structure is provided by secondary structural elements that are hydrogen bonds within the molecule and this leads to several recognizable domains of secondary structure like hairpin loops, bulges, and internal loops
5.
Ligand (biochemistry)
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In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein, the binding typically results in a change of conformation of the target protein. In DNA-ligand binding studies, the ligand can be a molecule, ion. The relationship between ligand and binding partner is a function of charge, hydrophobicity, and molecular structure, the instance of binding occurs over an infinitesimal range of time and space, so the rate constant is usually a very small number. Binding occurs by intermolecular forces, such as bonds, hydrogen bonds. The association of docking is actually reversible through dissociation, measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems. In contrast to the definition of ligand in metalorganic and inorganic chemistry, in biochemistry it is whether the ligand generally binds at a metal site. In general, the interpretation of ligand is contextual with regards to what sort of binding has been observed, the etymology stems from ligare, which means to bind. Ligand binding to a receptor protein alters the chemical conformation by affecting the shape orientation. The conformation of a receptor protein composes the functional state, ligands include substrates, inhibitors, activators, and neurotransmitters. The rate of binding is called affinity, and this measurement typifies a tendency or strength of the effect, binding affinity is actualized not only by host-guest interactions, but also by solvent effects that can play a dominant, steric role which drives non-covalent binding in solution. The solvent provides an environment for the ligand and receptor to adapt. Radioligands are radioisotope labeled compounds are used in vivo as tracers in PET studies, the interaction of most ligands with their binding sites can be characterized in terms of a binding affinity. In general, high-affinity binding results in a degree of occupancy for the ligand at its receptor binding site than is the case for low-affinity binding. A ligand that can bind to a receptor, alter the function of the receptor, high-affinity ligand binding implies that a relatively low concentration of a ligand is adequate to maximally occupy a ligand-binding site and trigger a physiological response. The lower the Ki concentration is, the more likely there will be a reaction between the pending ion and the receptive antigen. In the example shown to the right, two different ligands bind to the receptor binding site. Only one of the agonists shown can maximally stimulate the receptor and, thus, an agonist that can only partially activate the physiological response is called a partial agonist
6.
Molecule
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A molecule is an electrically neutral group of two or more atoms held together by chemical bonds. Molecules are distinguished from ions by their lack of electrical charge, however, in quantum physics, organic chemistry, and biochemistry, the term molecule is often used less strictly, also being applied to polyatomic ions. In the kinetic theory of gases, the molecule is often used for any gaseous particle regardless of its composition. According to this definition, noble gas atoms are considered molecules as they are in fact monoatomic molecules. A molecule may be homonuclear, that is, it consists of atoms of one element, as with oxygen, or it may be heteronuclear. Atoms and complexes connected by non-covalent interactions, such as hydrogen bonds or ionic bonds, are not considered single molecules. Molecules as components of matter are common in organic substances and they also make up most of the oceans and atmosphere. Also, no typical molecule can be defined for ionic crystals and covalent crystals, the theme of repeated unit-cellular-structure also holds for most condensed phases with metallic bonding, which means that solid metals are also not made of molecules. In glasses, atoms may also be together by chemical bonds with no presence of any definable molecule. The science of molecules is called molecular chemistry or molecular physics, in practice, however, this distinction is vague. In molecular sciences, a molecule consists of a system composed of two or more atoms. Polyatomic ions may sometimes be thought of as electrically charged molecules. The term unstable molecule is used for very reactive species, i. e, according to Merriam-Webster and the Online Etymology Dictionary, the word molecule derives from the Latin moles or small unit of mass. Molecule – extremely minute particle, from French molécule, from New Latin molecula, diminutive of Latin moles mass, a vague meaning at first, the vogue for the word can be traced to the philosophy of Descartes. The definition of the molecule has evolved as knowledge of the structure of molecules has increased, earlier definitions were less precise, defining molecules as the smallest particles of pure chemical substances that still retain their composition and chemical properties. Molecules are held together by covalent bonding or ionic bonding. Several types of non-metal elements exist only as molecules in the environment, for example, hydrogen only exists as hydrogen molecule. A molecule of a compound is made out of two or more elements, a covalent bond is a chemical bond that involves the sharing of electron pairs between atoms
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Ion
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An ion is an atom or a molecule in which the total number of electrons is not equal to the total number of protons, giving the atom or molecule a net positive or negative electrical charge. Ions can be created, by chemical or physical means. In chemical terms, if an atom loses one or more electrons. If an atom gains electrons, it has a net charge and is known as an anion. Ions consisting of only a single atom are atomic or monatomic ions, because of their electric charges, cations and anions attract each other and readily form ionic compounds, such as salts. In the case of ionization of a medium, such as a gas, which are known as ion pairs are created by ion impact, and each pair consists of a free electron. The word ion comes from the Greek word ἰόν, ion, going and this term was introduced by English physicist and chemist Michael Faraday in 1834 for the then-unknown species that goes from one electrode to the other through an aqueous medium. Faraday also introduced the words anion for a charged ion. In Faradays nomenclature, cations were named because they were attracted to the cathode in a galvanic device, arrhenius explanation was that in forming a solution, the salt dissociates into Faradays ions. Arrhenius proposed that ions formed even in the absence of an electric current, ions in their gas-like state are highly reactive, and do not occur in large amounts on Earth, except in flames, lightning, electrical sparks, and other plasmas. These gas-like ions rapidly interact with ions of charge to give neutral molecules or ionic salts. These stabilized species are commonly found in the environment at low temperatures. A common example is the present in seawater, which are derived from the dissolved salts. Electrons, due to their mass and thus larger space-filling properties as matter waves, determine the size of atoms. Thus, anions are larger than the parent molecule or atom, as the excess electron repel each other, as such, in general, cations are smaller than the corresponding parent atom or molecule due to the smaller size of its electron cloud. One particular cation contains no electrons, and thus consists of a single proton - very much smaller than the parent hydrogen atom. Since the electric charge on a proton is equal in magnitude to the charge on an electron, an anion, from the Greek word ἄνω, meaning up, is an ion with more electrons than protons, giving it a net negative charge. A cation, from the Greek word κατά, meaning down, is an ion with fewer electrons than protons, there are additional names used for ions with multiple charges
8.
Chemical bond
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A chemical bond is a lasting attraction between atoms that enables the formation of chemical compounds. The bond may result from the force of attraction between atoms with opposite charges, or through the sharing of electrons as in the covalent bonds. Since opposite charges attract via an electromagnetic force, the negatively charged electrons that are orbiting the nucleus. An electron positioned between two nuclei will be attracted to both of them, and the nuclei will be attracted toward electrons in this position and this attraction constitutes the chemical bond. This phenomenon limits the distance between nuclei and atoms in a bond, in general, strong chemical bonding is associated with the sharing or transfer of electrons between the participating atoms. All bonds can be explained by quantum theory, but, in practice, simplification rules allow chemists to predict the strength, directionality, the octet rule and VSEPR theory are two examples. Electrostatics are used to describe bond polarities and the effects they have on chemical substances, a chemical bond is an attraction between atoms. This attraction may be seen as the result of different behaviors of the outermost or valence electrons of atoms and these behaviors merge into each other seamlessly in various circumstances, so that there is no clear line to be drawn between them. However it remains useful and customary to differentiate different types of bond, which result in different properties of condensed matter. In the simplest view of a covalent bond, one or more electrons are drawn into the space between the two atomic nuclei, energy is released by bond formation. This is not as a reduction in energy, because the attraction of the two electrons to the two protons is offset by the electron-electron and proton-proton repulsions. In a polar covalent bond, one or more electrons are shared between two nuclei. Such weak intermolecular bonds give organic molecular substances, such as waxes and oils, their soft bulk character, also, the melting points of such covalent polymers and networks increase greatly. In a simplified view of a bond, the bonding electron is not shared at all. In this type of bond, the atomic orbital of one atom has a vacancy which allows the addition of one or more electrons. These newly added electrons potentially occupy a lower energy-state than they experience in a different atom, thus, one nucleus offers a more tightly bound position to an electron than does another nucleus, with the result that one atom may transfer an electron to the other. This transfer causes one atom to assume a net charge. The bond then results from electrostatic attraction between atoms and the atoms become positive or negatively charged ions, ionic bonds may be seen as extreme examples of polarization in covalent bonds
9.
Chemical equilibrium
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In a chemical reaction, chemical equilibrium is the state in which both reactants and products are present in concentrations which have no further tendency to change with time. Usually, this results when the forward reaction proceeds at the same rate as the reverse reaction. The reaction rates of the forward and backward reactions are not zero. Thus, there are no net changes in the concentrations of the reactant, such a state is known as dynamic equilibrium. The concept of chemical equilibrium was developed after Berthollet found that chemical reactions are reversible. For any reaction mixture to exist at equilibrium, the rates of the forward and backward reactions are equal, conversely the equilibrium position is said to be far to the left if hardly any product is formed from the reactants. Since at equilibrium forward and backward rates are equal, k + α β = k − σ τ, K c = k + k − = σ τ α β By convention the products form the numerator. Equality of forward and backward reaction rates, however, is a condition for chemical equilibrium. Adding a catalyst will affect both the reaction and the reverse reaction in the same way and will not have an effect on the equilibrium constant. The catalyst will speed up both reactions thereby increasing the speed at which equilibrium is reached, although the macroscopic equilibrium concentrations are constant in time, reactions do occur at the molecular level. This is an example of dynamic equilibrium, equilibria, like the rest of thermodynamics, are statistical phenomena, averages of microscopic behavior. Le Châteliers principle gives an idea of the behavior of a system when changes to its reaction conditions occur. If a dynamic equilibrium is disturbed by changing the conditions, the position of equilibrium moves to partially reverse the change. For example, adding more S from the outside will cause an excess of products, and this can also be deduced from the equilibrium constant expression for the reaction, K = If increases must increase and CH 3CO−2 must decrease. The H2O is left out, as it is the solvent and its concentration remains high, a quantitative version is given by the reaction quotient. J. W. Gibbs suggested in 1873 that equilibrium is attained when the Gibbs free energy of the system is at its minimum value, what this means is that the derivative of the Gibbs energy with respect to reaction coordinate vanishes, signalling a stationary point. This derivative is called the reaction Gibbs energy and corresponds to the difference between the chemical potentials of reactants and products at the composition of the reaction mixture and this criterion is both necessary and sufficient. If a mixture is not at equilibrium, the liberation of the excess Gibbs energy is the force for the composition of the mixture to change until equilibrium is reached
10.
Chemical affinity
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In chemical physics and physical chemistry, chemical affinity is the electronic property by which dissimilar chemical species are capable of forming chemical compounds. Chemical affinity can also refer to the tendency of an atom or compound to combine by chemical reaction with atoms or compounds of unlike composition, the idea of affinity is extremely old. Many attempts have been made at identifying its origins, the majority of such attempts, however, except in a general manner, end in futility since affinities lie at the basis of all magic, thereby pre-dating science. Physical chemistry, however, was one of the first branches of science to study, the name affinitas was first used in the sense of chemical relation by German philosopher Albertus Magnus near the year 1250. Later, those as Robert Boyle, John Mayow, Johann Glauber, Isaac Newton, the term affinity has been used figuratively since c.1600 in discussions of structural relationships in chemistry, philology, etc. and reference to natural attraction is from 1616. Chemical affinity, historically, has referred to the force that causes chemical reactions, as well as, more generally, and earlier, the ″tendency to combine″ of any pair of substances. The broad definition, used throughout history, is that chemical affinity is that whereby substances enter into or resist decomposition. Antoine Lavoisier, in his famed 1789 Traité Élémentaire de Chimie, refers to Bergman’s work, according to Prigogine, the term was introduced and developed by Théophile de Donder. Goethe used the concept in his novel Elective Affinities, the affinity concept was very closely linked to the visual representation of substances on a table. The first-ever affinity table, which was based on displacement reactions, was published in 1718 by the French chemist Étienne François Geoffroy, crucially, the table was the central graphic tool used to teach chemistry to students and its visual arrangement was often combined with other kinds diagrams. Joseph Black, for example, used the table in combination with chiastic, Affinity tables were used throughout Europe until the early 19th century when they were displaced by affinity concepts introduced by Claude Berthollet. In chemical physics and physical chemistry, chemical affinity is the property by which dissimilar chemical species are capable of forming chemical compounds. Chemical affinity can also refer to the tendency of an atom or compound to combine by chemical reaction with atoms or compounds of unlike composition, in modern terms, we relate affinity to the phenomenon whereby certain atoms or molecules have the tendency to aggregate or bond. In this antiquated context, chemical affinity is sometimes synonymous with the term magnetic attraction. Many writings, up until about 1925, also refer to a law of chemical affinity, ilya Prigogine summarized the concept of affinity, saying, All chemical reactions drive the system to a state of equilibrium in which the affinities of the reactions vanish. The present IUPAC definition is that affinity A is the partial derivative of Gibbs free energy G with respect to extent of reaction ξ at constant pressure and temperature. It follows that affinity is positive for spontaneous reactions, in 1923, the Belgian mathematician and physicist Théophile de Donder derived a relation between affinity and the Gibbs free energy of a chemical reaction. This definition is useful for quantifying the factors responsible both for the state of systems, and for changes of state of non-equilibrium systems
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Biomolecule
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A more general name for this class of material is biological materials. Biomolecules are usually endogenous but may also be exogenous, for example, pharmaceutical drugs may be natural products or semisynthetic or they may be totally synthetic. Biology and its subsets of biochemistry and molecular biology study biomolecules, most biomolecules are organic compounds, and just four elements—oxygen, carbon, hydrogen, and nitrogen—make up 96% of the human bodys mass. But many other elements, such as the various biometals, are present in small amounts, examples of these include cytidine, uridine, adenosine, guanosine, thymidine and inosine. Nucleosides can be phosphorylated by specific kinases in the cell, producing nucleotides, both DNA and RNA are polymers, consisting of long, linear molecules assembled by polymerase enzymes from repeating structural units, or monomers, of mononucleotides. DNA uses the deoxynucleotides C, G, A, and T, while RNA uses the ribonucleotides C, G, A, modified bases are fairly common, as found in ribosomal RNA or transfer RNAs or for discriminating the new from old strands of DNA after replication. Each nucleotide is made of a nitrogenous base, a pentose. They contain carbon, nitrogen, oxygen, hydrogen and phosphorus and they serve as sources of chemical energy, participate in cellular signaling, and are incorporated into important cofactors of enzymatic reactions. DNA structure is dominated by the double helix formed by Watson-Crick base-pairing of C with G and A with T. This is known as B-form DNA, and is overwhelmingly the most favorable and common state of DNA, its highly specific and stable base-pairing is the basis of reliable genetic information storage. DNA can sometimes occur as single strands or as A-form or Z-form helices, RNA, in contrast, forms large and complex 3D tertiary structures reminiscent of proteins, as well as the loose single strands with locally folded regions that constitute messenger RNA molecules. Those RNA structures contain many stretches of A-form double helix, connected into definite 3D arrangements by single-stranded loops, bulges, examples are tRNA, ribosomes, ribozymes, and riboswitches. Monosaccharides are the simplest form of carbohydrates with only one simple sugar and they essentially contain an aldehyde or ketone group in their structure. The presence of an group in a monosaccharide is indicated by the prefix aldo-. Similarly, a group is denoted by the prefix keto-. Examples of monosaccharides are the hexoses glucose, fructose, and galactose and pentoses, ribose, most saccharides eventually provide fuel for cellular respiration. Disaccharides are formed when two monosaccharides, or two simple sugars, form a bond with removal of water. They can be hydrolyzed to yield their saccharin building blocks by boiling with dilute acid or reacting them with appropriate enzymes, examples of disaccharides include sucrose, maltose, and lactose
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Active site
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In biology, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of residues that form bonds with the substrate. The active site is usually a groove or pocket of the enzyme which can be located in a tunnel within the enzyme. An active site can catalyse a reaction repeatedly as its residues are not altered at the end of the reaction, usually, an enzyme molecule has only one active site, and the active site fits with one specific type of substrate. An active site contains a site that binds the substrate. Residues in the site form hydrogen bonds, hydrophobic interactions. In order to function, the site needs to be in a specific conformation. A tighter fit between a site and the substrate molecule is believed to increase efficiency of a reaction. Most enzymes have deeply buried active sites, which can be accessed by a substrate via access channels, there are two proposed models of how enzymes fit to their specific substrate, the lock and key model and the induced fit model. Emil Fischers lock and key model assumes that the site is a perfect fit for a specific substrate. Daniel Koshlands theory of enzyme-substrate binding is that the active site, the induced fit model is a development of the lock-and-key model and assumes that an active site is flexible and it changes shape until the substrate is completely bound. The substrate is thought to induce a change in the shape of the active site, the hypothesis also predicts that the presence of certain residues in the active site will encourage the enzyme to locate the correct substrate. Conformational changes may occur as the substrate is bound. After the products of the move away from the enzyme. Once the substrate is bound and oriented in the active site, the residues of the catalytic site are typically very close to the binding site, and some residues can have dual-roles in both binding and catalysis. Catalytic residues of the site interact with the substrate to lower the energy of a reaction. They do this by a number of different mechanisms, firstly, they can act as donors or acceptors of protons or other groups on the substrate to facilitate the reaction. They can also form electrostatic interactions to stabilise charge buildup on the state or leaving group
13.
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
14.
Reaction mechanism
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In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs. A chemical mechanism is a conjecture that tries to describe in detail what takes place at each stage of an overall chemical reaction. The detailed steps of a reaction are not observable in most cases and it also describes each reactive intermediate, activated complex, and transition state, and which bonds are broken, and which bonds are formed. A complete mechanism must also explain the reason for the reactants and catalyst used, the stereochemistry observed in reactants and products, all products formed and the amount of each. The electron or arrow pushing method is used in illustrating a reaction mechanism, for example. A reaction mechanism must also account for the order in which molecules react, often what appears to be a single-step conversion is in fact a multistep reaction. Reaction intermediates are often free radicals or ions, the kinetics are explained in terms of the energy needed for the conversion of the reactants to the proposed transition states. Information about the mechanism of a reaction is provided by the use of chemical kinetics to determine the rate equation. Consider the following reaction for example, CO + NO2 → CO2 + NO In this case and this form suggests that the rate-determining step is a reaction between two molecules of NO2. The elementary steps should add up to the original reaction, when determining the overall rate law for a reaction, the slowest step is the step that determines the reaction rate. Because the first step is the slowest step, it is the rate-determining step, because it involves the collision of two NO2 molecules, it is a bimolecular reaction with a rate law of r = k 2. Other reactions may have mechanisms of several consecutive steps, in organic chemistry, one of the first reaction mechanisms proposed was that for the benzoin condensation, put forward in 1903 by A. J. Lapworth. There are also more complex such as chain reactions, in which the propagation steps of the chain form a closed cycle. A correct reaction mechanism is an important part of accurate predictive modeling, for many combustion and plasma systems, detailed mechanisms are not available or require development. Rate constants or thermochemical data are not available in the literature. Computational chemistry methods can also be used to calculate potential energy surfaces for reactions, molecularity in chemistry is the number of colliding molecular entities that are involved in a single reaction step. A reaction step involving one molecular entity is called unimolecular, a reaction step involving two molecular entities is called bimolecular. A reaction step involving three molecular entities is called termolecular
15.
Product (chemistry)
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Products are the species formed from chemical reactions. During a chemical reaction reactants are transformed into products after passing through an energy transition state. This process results in the consumption of the reactants, when represented in chemical equations products are by convention drawn on the right-hand side, even in the case of reversible reactions. The properties of such as their energies help determine several characteristics of a chemical reaction such as whether the reaction is exergonic or endergonic. Additionally the properties of a product can make it easier to extract and purify following a chemical reaction, reactants are molecular materials used to create chemical reactions. The atoms arent created or destroyed, the materials are reactive and reactants are rearranging during a chemical reaction. Here is an example of reactants, CH4 + O2, a non-example is CO2 + H2O or energy. Much of chemistry research is focused on the synthesis and characterization of beneficial products, as well as the detection, other fields include natural product chemists who isolate products created by living organisms and then characterize and study these products. The products of a chemical reaction influence several aspects of the reaction, if the products are lower in energy than the reactants, then the reaction will give off excess energy making it an exergonic reaction. Such reactions are thermodynamically favorable and tend to happen on their own, if the kinetics of the reaction are high enough, however, then the reaction may occur too slowly to be observed, or not even occur at all. If the products are higher in energy than the reactants then the reaction will require energy to be performed and is therefore an endergonic reaction. Additionally if the product is less stable than a reactant, then Lefflers assumption holds that the state will more closely resemble the product than the reactant. Ever since the mid nineteenth century chemists have been preoccupied with synthesizing chemical products. Much of synthetic chemistry is concerned with the synthesis of new chemicals as occurs in the design and creation of new drugs, in biochemistry, enzymes act as biological catalysts to convert substrate to product. For example, the products of the enzyme lactase are galactose and glucose, S + E → P + E Where S is substrate, P is product and E is enzyme. Some enzymes display a form of promiscuity where they convert a single substrate into multiple different products and it occurs when the reaction occurs via a high energy transition state that can be resolved into a variety of different chemical products. Some enzymes are inhibited by the product of their reaction binds to the enzyme and this can be important in the regulation of metabolism as a form of negative feedback controlling metabolic pathways. Product inhibition is also an important topic in biotechnology, as overcoming this effect can increase the yield of a product, Chemical reaction Substrate Reagent Precursor Catalyst Enzyme Product Derivative Chemical equilibrium Second law of thermodynamics
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Peptide
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Peptides are biologically occurring short chains of amino acid monomers linked by peptide bonds. The covalent chemical bonds are formed when the group of one amino acid reacts with the amine group of another. The shortest peptides are dipeptides, consisting of 2 amino acids joined by a peptide bond, followed by tripeptides, tetrapeptides. A polypeptide is a long, continuous, and unbranched peptide chain, hence, peptides fall under the broad chemical classes of biological oligomers and polymers, alongside nucleic acids, oligosaccharides and polysaccharides, etc. Peptides are distinguished from proteins on the basis of size, all peptides except cyclic peptides have an N-terminal and C-terminal residue at the end of the peptide. Ribosomal peptides Ribosomal peptides are synthesized by translation of mRNA and they are often subjected to proteolysis to generate the mature form. These function, typically in higher organisms, as hormones and signaling molecules, some organisms produce peptides as antibiotics, such as microcins. Since they are translated, the amino acid residues involved are restricted to those utilized by the ribosome, however, these peptides frequently have posttranslational modifications such as phosphorylation, hydroxylation, sulfonation, palmitoylation, glycosylation and disulfide formation. In general, they are linear, although lariat structures have been observed, more exotic manipulations do occur, such as racemization of L-amino acids to D-amino acids in platypus venom. Nonribosomal peptides Nonribosomal peptides are assembled by enzymes that are specific to each peptide, the most common non-ribosomal peptide is glutathione, which is a component of the antioxidant defenses of most aerobic organisms. Other nonribosomal peptides are most common in organisms, plants. These complexes are often out in a similar fashion. These peptides are often cyclic and can have highly complex cyclic structures, since the system is closely related to the machinery for building fatty acids and polyketides, hybrid compounds are often found. The presence of oxazoles or thiazoles often indicates that the compound was synthesized in this fashion, Peptones See also Tryptone Peptones are derived from animal milk or meat digested by proteolysis. In addition to containing small peptides, the material includes fats, metals, salts, vitamins. Peptones are used in nutrient media for growing bacteria and fungi, Peptide fragments Peptide fragments refer to fragments of proteins that are used to identify or quantify the source protein. Peptides received prominence in molecular biology for several reasons, the first is that peptides allow the creation of peptide antibodies in animals without the need of purifying the protein of interest. This involves synthesizing antigenic peptides of sections of the protein of interest and these will then be used to make antibodies in a rabbit or mouse against the protein
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Transcription factor
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In molecular biology, a transcription factor is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. In turn, this helps to regulate the expression of genes near that sequence, transcription factors work alone or with other proteins in a complex, by promoting, or blocking the recruitment of RNA polymerase to specific genes. A defining feature of transcription factors is that they contain at least one DNA-binding domain, transcription factors are usually classified into different families based on their DBDs. Transcription factors are essential for the regulation of expression and are, as a consequence. The number of factors found within an organism increases with genome size. Therefore, approximately 10% of genes in the code for transcription factors. Hence, the use of a subset of the approximately 2000 human transcription factors easily accounts for the unique regulation of each gene in the human genome during development. Transcription factors bind to either enhancer or promoter regions of DNA adjacent to the genes that they regulate, depending on the transcription factor, the transcription of the adjacent gene is either up- or down-regulated. Transcription factors use a variety of mechanisms for the regulation of gene expression and these mechanisms include, stabilize or block the binding of RNA polymerase to DNA catalyze the acetylation or deacetylation of histone proteins. The transcription factor can either do this directly or recruit other proteins with this catalytic activity and they bind to the DNA and help initiate a program of increased or decreased gene transcription. As such, they are vital for important cellular processes. Many of these GTFs do not actually bind DNA, but rather are part of the large transcription preinitiation complex that interacts with RNA polymerase directly, the most common GTFs are TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. The preinitiation complex binds to regions of DNA upstream to the gene that they regulate. Other transcription factors regulate the expression of various genes by binding to enhancer regions of DNA adjacent to regulated genes. These transcription factors are critical to making sure that genes are expressed in the cell at the right time and in the right amount. Many transcription factors in multicellular organisms are involved in development, the Hox transcription factor family, for example, is important for proper body pattern formation in organisms as diverse as fruit flies to humans. Another example is the transcription factor encoded by the Sex-determining Region Y gene, cells can communicate with each other by releasing molecules that produce signaling cascades within another receptive cell. If the signal requires upregulation or downregulation of genes in the recipient cell, the estrogen receptor then goes to the cells nucleus and binds to its DNA-binding sites, changing the transcriptional regulation of the associated genes
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Antibody
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An antibody, also known as an immunoglobulin, is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as bacteria and viruses. The antibody recognizes a molecule of the harmful agent, called an antigen. Each tip of the Y of an antibody contains a paratope that is specific for one particular epitope on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or a cell for attack by other parts of the immune system. Depending on the antigen, the binding may impede the process causing the disease or may activate macrophages to destroy the foreign substance. The ability of an antibody to communicate with the components of the immune system is mediated via its Fc region. The production of antibodies is the function of the humoral immune system. Antibodies are secreted by B cells of the immune system. In most cases, interaction of the B cell with a T helper cell is necessary to produce full activation of the B cell and, therefore, soluble antibodies are released into the blood and tissue fluids, as well as many secretions to continue to survey for invading microorganisms. Antibodies are glycoproteins belonging to the immunoglobulin superfamily and they constitute most of the gamma globulin fraction of the blood proteins. They are typically made of basic structural units—each with two heavy chains and two small light chains. There are several different types of heavy chains that define the five different types of crystallisable fragments that may be attached to the antigen-binding fragments. The five different types of Fc regions allow antibodies to be grouped into five isotypes, each Fc region of a particular antibody isotype is able to bind to its specific Fc Receptor, thus allowing the antigen-antibody complex to mediate different roles depending on which FcR it binds. The ability of an antibody to bind to its corresponding FcR is further modulated by the structure of the present at conserved sites within its Fc region. The ability of antibodies to bind to FcRs helps to direct the immune response for each different type of foreign object they encounter. For example, IgE is responsible for an allergic response consisting of mast cell degranulation, igEs Fab paratope binds to allergic antigen, for example house dust mite particles, while its Fc region binds to Fc receptor ε. The allergen-IgE-FcRε interaction mediates allergic signal transduction to induce conditions such as asthma and this region is known as the hypervariable region. Each of these variants can bind to a different antigen and this enormous diversity of antibody paratopes on the antigen-binding fragments allows the immune system to recognize an equally wide variety of antigens
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Antigen
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In immunology, an antigen is a molecule capable of inducing an immune response on the part of the host organism, though sometimes antigens can be part of the host itself. In other words, an antigen is any substance that causes a system to produce antibodies against it. In most cases, an antibody can bind one specific antigen, in some instances, however. An antigen is a molecule that binds to Ag-specific receptors, Antigens are usually peptides, polysaccharides or lipids. In general, molecules other than peptides qualify as antigens but not as immunogens since they cannot elicit a response on their own. Furthermore, for a peptide to induce a response it must be a large enough size. The term antigen originally described a structural molecule that specifically to an antibody. It expanded to refer to any molecule or a molecular fragment that can be recognized by highly variable antigen receptors of the adaptive immune system. The antigen may originate from within the body or from the external environment, antigen presenting cells present antigens in the form of peptides on histocompatibility molecules. The T cells of the immune system recognize the antigens. Depending on the antigen and the type of the histocompatibility molecule, for T-Cell Receptor recognition, the peptide must be processed into small fragments inside the cell and presented by a major histocompatibility complex. The antigen cannot elicit the immune response without the help of an immunologic adjuvant, similarly, the adjuvant component of vaccines plays an essential role in the activation of the innate immune system. An immunogen is a substance that is able to trigger a humoral and/or cell-mediated immune response and it first initiates an innate immune response, which then causes the activation of the adaptive immune response. An antigen binds the highly variable immunoreceptor products once these have been generated, all immunogen molecules are also antigens, although the reverse is not true. At the molecular level, an antigen can be characterized by its ability to bind to an antibodys variable Fab region, different antibodies have the potential to discriminate among specific epitopes present on the antigen surface. A hapten is a molecule that changes the structure of an antigenic epitope. In order to induce a response, it needs to be attached to a large carrier molecule such as a protein. Antigens are usually proteins and polysaccharides, and less frequently, lipids and this includes parts of bacteria, viruses, and other microorganisms
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Machine learning
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Machine learning is the subfield of computer science that, according to Arthur Samuel in 1959, gives computers the ability to learn without being explicitly programmed. Machine learning is related to computational statistics, which also focuses on prediction-making through the use of computers. It has strong ties to optimization, which delivers methods, theory. Machine learning is sometimes conflated with data mining, where the latter subfield focuses more on data analysis and is known as unsupervised learning. Machine learning can also be unsupervised and be used to learn and establish baseline behavioral profiles for various entities, tom M. be replaced with the question Can machines do what we can do. In the proposal he explores the characteristics that could be possessed by a thinking machine. Machine learning tasks are typically classified into three categories, depending on the nature of the learning signal or feedback available to a learning system. These are Supervised learning, The computer is presented with example inputs and their outputs, given by a teacher. Unsupervised learning, No labels are given to the learning algorithm, unsupervised learning can be a goal in itself or a means towards an end. Reinforcement learning, A computer program interacts with an environment in which it must perform a certain goal. The program is provided feedback in terms of rewards and punishments as it navigates its problem space, between supervised and unsupervised learning is semi-supervised learning, where the teacher gives an incomplete training signal, a training set with some of the target outputs missing. Transduction is a case of this principle where the entire set of problem instances is known at learning time. Among other categories of machine learning problems, learning to learn learns its own inductive bias based on previous experience and this is typically tackled in a supervised way. Spam filtering is an example of classification, where the inputs are email messages, in regression, also a supervised problem, the outputs are continuous rather than discrete. In clustering, a set of inputs is to be divided into groups, unlike in classification, the groups are not known beforehand, making this typically an unsupervised task. Density estimation finds the distribution of inputs in some space, dimensionality reduction simplifies inputs by mapping them into a lower-dimensional space. Topic modeling is a problem, where a program is given a list of human language documents and is tasked to find out which documents cover similar topics. As a scientific endeavour, machine learning grew out of the quest for artificial intelligence, already in the early days of AI as an academic discipline, some researchers were interested in having machines learn from data
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PubMed Identifier
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PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez system of information retrieval, from 1971 to 1997, MEDLINE online access to the MEDLARS Online computerized database primarily had been through institutional facilities, such as university libraries. PubMed, first released in January 1996, ushered in the era of private, free, home-, the PubMed system was offered free to the public in June 1997, when MEDLINE searches via the Web were demonstrated, in a ceremony, by Vice President Al Gore. Information about the journals indexed in MEDLINE, and available through PubMed, is found in the NLM Catalog. As of 5 January 2017, PubMed has more than 26.8 million records going back to 1966, selectively to the year 1865, and very selectively to 1809, about 500,000 new records are added each year. As of the date,13.1 million of PubMeds records are listed with their abstracts. In 2016, NLM changed the system so that publishers will be able to directly correct typos. Simple searches on PubMed can be carried out by entering key aspects of a subject into PubMeds search window, when a journal article is indexed, numerous article parameters are extracted and stored as structured information. Such parameters are, Article Type, Secondary identifiers, Language, publication type parameter enables many special features. As these clinical girish can generate small sets of robust studies with considerable precision, since July 2005, the MEDLINE article indexing process extracts important identifiers from the article abstract and puts those in a field called Secondary Identifier. The secondary identifier field is to store numbers to various databases of molecular sequence data, gene expression or chemical compounds. For clinical trials, PubMed extracts trial IDs for the two largest trial registries, ClinicalTrials. gov and the International Standard Randomized Controlled Trial Number Register, a reference which is judged particularly relevant can be marked and related articles can be identified. If relevant, several studies can be selected and related articles to all of them can be generated using the Find related data option, the related articles are then listed in order of relatedness. To create these lists of related articles, PubMed compares words from the title and abstract of each citation, as well as the MeSH headings assigned, using a powerful word-weighted algorithm. The related articles function has been judged to be so precise that some researchers suggest it can be used instead of a full search, a strong feature of PubMed is its ability to automatically link to MeSH terms and subheadings. Examples would be, bad breath links to halitosis, heart attack to myocardial infarction, where appropriate, these MeSH terms are automatically expanded, that is, include more specific terms. Terms like nursing are automatically linked to Nursing or Nursing and this important feature makes PubMed searches automatically more sensitive and avoids false-negative hits by compensating for the diversity of medical terminology. The My NCBI area can be accessed from any computer with web-access, an earlier version of My NCBI was called PubMed Cubby
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Catalytic triad
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A catalytic triad refers to the three amino acid residues that function together at the centre of the active site of some hydrolase and transferase enzymes. An Acid-Base-Nucleophile triad is a motif for generating a nucleophilic residue for covalent catalysis. The nucleophile is most commonly a serine or cysteine amino acid, as well as divergent evolution of function, catalytic triads show some of the best examples of convergent evolution. Chemical constraints on catalysis have led to the same solution independently evolving in at least 23 separate superfamilies. Their mechanism of action is one of the best studied in biochemistry. The enzymes trypsin and chymotrypsin were first purified in the 1930s, a serine in each of trypsin and chymotrypsin was identified as the catalytic nucleophile in the 1950s. The structure of chymotrypsin was solved by X-ray crystallography in the 1960s, other proteases were sequenced and aligned to reveal a family of related proteases, now called the S1 family. Simultaneously, the structures of the evolutionarily unrelated papain and subtilisin proteases were found to contain analogous triads, the charge-relay mechanism for the activation of the nucleophile by the other triad members was proposed in the late 1960s. As more protease structures were solved by X-ray crystallography in the 1970s and 80s, understanding how chemical constraints on evolution led to the convergence of so many enzyme families on the same triad geometries has developed in the 2010s. The massive body of work on the charge-relay, covalent catalysis used by catalytic triads has led to the mechanism being the best characterised in all of biochemistry. Enzymes that contain an catalytic triad use it for one of two types, either to split a substrate or to transfer one portion of a substrate over to a second substrate. Triads are an inter-dependent set of residues in the site of an enzyme. These triad residues act together to make the nucleophile member highly reactive, catalytic triads perform covalent catalysis using a residue as a nucleophile. The reactivity of the residue is increased by the functional groups of the other triad members. The nucleophile is polarised and oriented by the base, which is itself bound, catalysis is performed in two stages. First, the nucleophile attacks the carbonyl carbon and forces the carbonyl oxygen to accept an electron. The build-up of negative charge on this intermediate is stabilized by an oxanion hole within the active site. The intermediate then collapses back to a carbonyl, ejecting the first half of the substrate, the ejection of this first leaving group is often aided by donation of a proton by the base
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Oxyanion hole
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An oxyanion hole is a pocket in the active site of an enzyme that stabilizes transition state negative charge on a deprotonated oxygen or alkoxide. The pocket typically consists of backbone amides or positively charged residues, stabilising the transition state lowers the activation energy necessary for the reaction, and so promotes catalysis. Additionally, it may allow for insertion or positioning of a substrate, enzymes that catalyse multi-step reactions can have multiple oxyanion holes that stabilise different transition states in the reaction. Enzyme catalysis Active site Transition state Serine proteases#Catalytic mechanism Albert Lehninger, et al
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Enzyme promiscuity
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Enzyme promiscuity is the ability of an enzyme to catalyse a fortuitous side reaction in addition to its main reaction. Although enzymes are remarkably specific catalysts, they can often perform side reactions in addition to their main and these promiscuous activities are usually slow relative to the main activity and are under neutral selection. An example of this is the atrazine chlorohydrolase from Pseudomonas sp, ADP which evolved from melamine deaminase, which has very small promiscuous activity towards atrazine, a man-made chemical. Enzymes are evolved to catalyse a reaction on a particular substrate with a high catalytic efficiency. Several theoretical models exist to predict the order of duplication and specialisation events, on the other, enzymes may evolve an increased secondary activity with little loss to the primary activity with little adaptive conflict. A study of three distinct hydrolases has shown the main activity is robust towards change, whereas the activities are more plastic. Specifically, selecting for an activity that is not the activity, does not initially diminish the main activity. The most recent and most clear cut example of evolution is the rise of bioremediating enzymes in the past 60 years. Due to the low number of amino acid changes, these provide an excellent model to investigate enzyme evolution in nature. This issue can be resolved thanks to ancestral reconstruction and this variability in ancestral specificity has not only been observed between different genes, but also within the same gene family. Antithetically, the ancestor before the split had a more pronounced isomaltose-like glucosidase activity. Roy Jensen in 1976 theorised that primordial enzymes had to be highly promiscuous in order for networks to assemble in a patchwork fashion. This primordial catalytic versatility was later lost in favour of highly catalytic specialised orthologous enzymes, as a consequence, many central-metabolic enzymes have structural homologues that diverged before the last universal common ancestor. Promiscuity is however not only a primordial trait, in fact it is very widespread property in modern genomes, a series of experiments have been conducted to assess the distribution of promiscuous enzyme activities in E. coli. In E. coli 21 out of 104 single-gene knockouts tested could be rescued by overexpressing a noncognate E. coli protein, similarly, overexpressing the ORF collection allowed E. coli to gain over an order of magnitude in resistance in 86 out 237 toxic environment. Homologues are sometimes known to display promiscuity towards each others main reactions, despite the divergence the homologues have a varying degree of reciprocal promiscuity, the differences in promiscuity are due to mechanisms involved, particularly the intermediate required. Examples of these are enzymes for primary and secondary metabolism in plants, a promiscuous activity is a non-native activity the enzyme did not evolve to do, but arises due to an accommodating conformation of the active site. When the specificity of enzyme was probed, it was found that it was selective against natural amino acids that were not phenylalanine
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Diffusion limited enzyme
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A Diffusion limited enzyme is an enzyme which catalyses a reaction so efficiently that the rate limiting step is that of substrate diffusion into the active site, or product diffusion out. This is also known as kinetic perfection or catalytic perfection, since the rate of catalysis of such enzymes is set by the diffusion-controlled reaction, it therefore represents an intrinsic, physical constraint on evolution. Diffusion limited perfect enzymes are very rare, most enzymes catalyse their reactions to a rate that is 1, 000-10,000 times slower than this limit. This is due to both the limitations of difficult reactions, and the evolutionary limitations that such high reaction rates do not confer any extra fitness. The theory of diffusion-controlled reaction was utilized by R. A. Alberty, Gordon Hammes, and Manfred Eigen to estimate the upper limit of enzyme-substrate reaction, according to their estimation, the upper limit of enzyme-substrate reaction was 109 M−1 s−1. To address such a paradox, Prof, the new upper limit found by Chou et al. for enzyme-substrate reaction was further discussed and analyzed by a series of follow-up studies. Kinetically perfect enzymes have a specificity constant, kcat/Km, on the order of 108 to 109 M−1 s−1, the rate of the enzyme-catalysed reaction is limited by diffusion and so the enzyme processes the substrate well before it encounters another molecule. Some enzymes operate with kinetics which are faster than diffusion rates, several mechanisms have been invoked to explain this phenomenon. Some proteins are believed to accelerate catalysis by drawing their substrate in, some invoke a quantum-mechanical tunneling explanation whereby a proton or an electron can tunnel through activation barriers, although proton tunneling remains a somewhat controversial idea. It is worth noting that there are not many kinetically perfect enzymes and this can be explained in terms of natural selection. An increase in speed may be favoured as it could confer some advantage to the organism. However, when the catalytic speed outstrips diffusion speed there is no advantage to increase the speed even further. The diffusion limit represents a physical constraint on evolution. Increasing the catalytic speed past the speed will not aid the organism in any way
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Cofactor (biochemistry)
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A cofactor is a non-protein chemical compound or metallic ion that is required for a proteins biological activity to happen. These proteins are enzymes, and cofactors can be considered helper molecules that assist in biochemical transformations. A coenzyme that is tightly or even covalently bound is termed a prosthetic group, the two subcategories under coenzyme are cosubstrates and prosthetic groups. Cosubstrates are transiently bound to the protein and will be released at some point, the prosthetic groups, on the other hand, are bound permanently to the protein. Both of them have the function, which is to facilitate the reaction of enzymes. Additionally, some sources also limit the use of the cofactor to inorganic substances. An inactive enzyme without the cofactor is called an apoenzyme, while the enzyme with cofactor is called a holoenzyme. Some enzymes or enzyme complexes require several cofactors, organic cofactors are often vitamins or made from vitamins. Many contain the nucleotide adenosine monophosphate as part of their structures, such as ATP, coenzyme A, FAD and this common structure may reflect a common evolutionary origin as part of ribozymes in an ancient RNA world. It has been suggested that the AMP part of the molecule can be considered to be a kind of handle by which the enzyme can grasp the coenzyme to switch it between different catalytic centers. Cofactors can be divided into two groups, organic cofactors, such as flavin or heme, and inorganic cofactors, such as the metal ions Mg2+, Cu+, Mn2+. Organic cofactors are sometimes divided into coenzymes and prosthetic groups. The term coenzyme refers specifically to enzymes and, as such, on the other hand, prosthetic group emphasizes the nature of the binding of a cofactor to a protein and, thus, refers to a structural property. Different sources give different definitions of coenzymes, cofactors. It should be noted that terms are often used loosely. However, the author could not arrive at a single all-encompassing definition of a coenzyme, the study of these cofactors falls under the area of bioinorganic chemistry. In nutrition, the list of essential trace elements reflects their role as cofactors, in humans this list commonly includes iron, magnesium, manganese, cobalt, copper, zinc, and molybdenum. Although chromium deficiency causes impaired glucose tolerance, no human enzyme that uses this metal as a cofactor has been identified, iodine is also an essential trace element, but this element is used as part of the structure of thyroid hormones rather than as an enzyme cofactor
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Enzyme catalysis
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Enzyme catalysis is the increase in the rate of a chemical reaction by the active site of a protein. The protein catalyst may be part of a complex, and/or may transiently or permanently associate with a Cofactor. Catalysis of biochemical reactions in the cell is vital due to the very low rates of the uncatalysed reactions at room temperature and pressure. A key driver of protein evolution is the optimization of such catalytic activities via protein dynamics, the mechanism of enzyme catalysis is similar in principle to other types of chemical catalysis. By providing an alternative reaction route the enzyme reduces the required to reach the highest energy transition state of the reaction. The reduction of activation increases the amount of reactant molecules that achieve a sufficient level of energy, such that they reach the activation energy. As with other catalysts, the enzyme is not consumed during the reaction but is recycled such that a single enzyme performs many rounds of catalysis, the favored model for the enzyme-substrate interaction is the induced fit model. The advantages of the induced fit mechanism arise due to the effect of strong enzyme binding. There are two different mechanisms of substrate binding, uniform binding, which has strong binding, and differential binding. The stabilizing effect of uniform binding increases both substrate and transition state binding affinity, while differential binding increases only transition state binding affinity, both are used by enzymes and have been evolutionarily chosen to minimize the activation energy of the reaction. It is important to clarify, however, that the induced fit concept cannot be used to rationalize catalysis and that is, the chemical catalysis is defined as the reduction of Ea‡ relative to Ea‡ in the uncatalyzed reaction in water. The induced fit only suggests that the barrier is lower in the form of the enzyme. Induced fit may be beneficial to the fidelity of molecular recognition in the presence of competition, →→→editor These conformational changes also bring catalytic residues in the active site close to the chemical bonds in the substrate that will be altered in the reaction. After binding takes place, one or more mechanisms of catalysis lowers the energy of the transition state. This effect is analogous to an increase in concentration of the reagents. The binding of the reagents to the enzyme gives the reaction intramolecular character, however, the situation might be more complex, since modern computational studies have established that traditional examples of proximity effects cannot be related directly to enzyme entropic effects. Also, the original proposal has been found to largely overestimate the contribution of orientation entropy to catalysis. Histidine is often the residue involved in these reactions, since it has a pKa close to neutral pH
28.
Allosteric regulation
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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
29.
Cooperativity
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This is referred to as cooperative binding. We also see cooperativity in large chain molecules made of identical subunits. This is referred to as subunit cooperativity, when a substrate binds to one enzymatic subunit, the rest of the subunits are stimulated and become active. Ligands can either have positive cooperativity, negative cooperativity, or non-cooperativity, an example of positive cooperativity is the binding of oxygen to hemoglobin. One oxygen molecule can bind to the iron of a heme molecule in each of the four chains of a hemoglobin molecule. The oxygen affinity of 3-oxy-hemoglobin is ~300 times greater than that of deoxy-hemoglobin and this behavior leads the affinity curve of hemoglobin to be sigmoidal, rather than hyperbolic as with the monomeric myoglobin. By the same process, the ability for hemoglobin to lose oxygen increases as fewer oxygen molecules are bound, an example of this occurring is the relationship between glyceraldehyde-3-phosphate and the enzyme glyceraldehyde-3-phosphate dehydrogenase. Homotropic cooperativity refers to the fact that the causing the cooperativity is the one that will be affected by it. Heterotropic cooperativity is where a third party substance causes the change in affinity, for example, unwinding of DNA involves cooperativity, Portions of DNA must unwind in order for DNA to carry out replication, transcription and recombination. The cooperative unit size is the number of adjacent bases that tend to unwind as a unit due to the effects of positive cooperativity. This phenomenon applies to other types of molecules as well, such as the folding and unfolding of proteins. Subunit cooperativity is measured on the relative scale known as Hills Constant, a simple and widely used model for molecular interactions is the Hill Equation. This provides a way to quantify cooperative binding by describing the fraction of saturated ligand binding sites as a function of the ligand concentration, in all of the above types of cooperativity, entropy plays a role. For example, in the case of oxygen binding to hemoglobin and this represents a state of higher entropy compared to a fourth oxygen having one available binding site. Thus, in transition from the unbound to the bound state, the first oxygen must overcome a larger entropy change than the last oxygen in order to bind to the hemoglobin
30.
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
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Protein superfamily
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A protein superfamily is the largest grouping of proteins for which common ancestry can be inferred. Usually this common ancestry is inferred from structural alignment and mechanistic similarity, sequence homology can then be deduced even if not apparent. Superfamilies typically contain several protein families which show sequence similarity within each family, the term protein clan is commonly used for protease superfamilies based on the MEROPS protease classification system. Superfamilies of proteins are identified using a number of methods, closely related members can be identified by different methods to those needed to group the most evolutionarily divergent members. Historically, the similarity of different amino acid sequences has been the most common method of inferring homology, amino acid sequence is typically more conserved than DNA sequence, so is a more sensitive detection method. Since some of the amino acids have similar properties, conservative mutations that interchange them are often neutral to function, the most conserved sequence regions of a protein often correspond to functionally important regions like catalytic sites and binding sites, since these regions are less tolerant to sequence changes. Using sequence similarity to infer homology has several limitations, there is no minimum level of sequence similarity guaranteed to produce identical structures. Over long periods of evolution, related proteins may show no sequence similarity to one another. Sequences with many insertions and deletions can also sometimes be difficult to align, in the PA clan of proteases, for example, not a single residue is conserved through the superfamily, not even those in the catalytic triad. Conversely, the families that make up a superfamily are defined on the basis of their sequence alignment. Nevertheless, sequence similarity is the most commonly used form of evidence to infer relatedness, in the absence of structural information, sequence similarity constrains the limits of which proteins can be assigned to a superfamily. Structure is much more conserved than sequence, such that proteins with highly similar structures can have entirely different sequences. Over very long timescales, very few residues show detectable amino acid sequence conservation, however secondary structural elements. Conformational changes of the structure may also be conserved, as is seen in the serpin superfamily. Consequently, protein structure can be used to detect homology between proteins even when no evidence of relatedness remains in their sequences. Structural alignment programs, such as DALI, use the 3D structure of a protein of interest to find proteins with similar folds, however, on rare occasions, related proteins may evolve to be structurally dissimilar and relatedness can only be inferred by other methods. The catalytic mechanism of enzymes within a superfamily is typically conserved, catalytic residues also tend to occur in the same order in the protein sequence. However, mechanism alone is not sufficient to infer relatedness, since some catalytic mechanisms have been convergently evolved multiple times independently, protein superfamilies represent the current limits of our ability to identify common ancestry
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Protein family
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A protein family is a group of evolutionarily-related proteins. In many cases a protein family has a gene family. The term protein family should not be confused with family as it is used in taxonomy, proteins in a family descend from a common ancestor and typically have similar three-dimensional structures, functions, and significant sequence similarity. The most important of these is sequence similarity since it is the strictest indicator of homology, there is a fairly well developed framework for evaluating the significance of similarity between a group of sequences using sequence alignment methods. Families are sometimes grouped together into larger clades called superfamilies based on structural and mechanistic similarity, currently, over 60,000 protein families have been defined, although ambiguity in the definition of protein family leads different researchers to wildly varying numbers. Other terms such as class, group, clan and sub-family have been coined over the years. A common usage is that superfamilies contain families which contain sub-families, hence a superfamily, such as the PA clan of proteases, has far lower sequence conservation than one of the families it contains, the C04 family. It is unlikely that an exact definition will be agreed and to it is up to the reader to discern exactly how these terms are being used in a particular context, since that time, it was found that many proteins comprise multiple independent structural and functional units or domains. Due to evolutionary shuffling, different domains in a protein have evolved independently and this has led, in recent years, to a focus on families of protein domains. A number of resources are devoted to identifying and cataloging such domains. Regions of each protein have differing functional constraints, for example, the active site of an enzyme requires certain amino acid residues to be precisely oriented in three dimensions. On the other hand, a protein–protein binding interface may consist of a surface with constraints on the hydrophobicity or polarity of the amino acid residues. These blocks are most commonly referred to as motifs, although other terms are used. Again, a number of online resources are devoted to identifying and cataloging protein motifs. According to current consensus, protein families arise in two ways, firstly, the separation of a parent species into two genetically isolated descendent species allows a gene/protein to independently accumulate variations in these two lineages. This results in a family of proteins, usually with conserved sequence motifs. Secondly, a gene duplication may create a copy of a gene. Because the original gene is able to perform its function
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Enzyme kinetics
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Enzyme kinetics is the study of the chemical reactions that are catalysed by enzymes. In enzyme kinetics, the rate is measured and the effects of varying the conditions of the reaction are investigated. Enzymes are usually protein molecules that manipulate other molecules — the enzymes substrates, kinetic studies on enzymes that only bind one substrate, such as triosephosphate isomerase, aim to measure the affinity with which the enzyme binds this substrate and the turnover rate. Some other examples of enzymes are phosphofructokinase and hexokinase, both of which are important for cellular respiration, when enzymes bind multiple substrates, such as dihydrofolate reductase, enzyme kinetics can also show the sequence in which these substrates bind and the sequence in which products are released. An example of enzymes that bind a single substrate and release multiple products are proteases, others join two substrates together, such as DNA polymerase linking a nucleotide to DNA. Although these mechanisms are often a series of steps, there is typically one rate-determining step that determines the overall kinetics. This rate-determining step may be a reaction or a conformational change of the enzyme or substrates. Knowledge of the structure is helpful in interpreting kinetic data. For example, the structure can suggest how substrates and products bind during catalysis, what changes occur during the reaction, not all biological catalysts are protein enzymes, RNA-based catalysts such as ribozymes and ribosomes are essential to many cellular functions, such as RNA splicing and translation. The main difference between ribozymes and enzymes is that RNA catalysts are composed of nucleotides, whereas enzymes are composed of amino acids, ribozymes also perform a more limited set of reactions, although their reaction mechanisms and kinetics can be analysed and classified by the same methods. The reaction catalysed by an enzyme uses exactly the same reactants, like other catalysts, enzymes do not alter the position of equilibrium between substrates and products. However, unlike uncatalysed chemical reactions, enzyme-catalysed reactions display saturation kinetics, the substrate concentration midway between these two limiting cases is denoted by KM. The two most important kinetic properties of an enzyme are how quickly the enzyme becomes saturated with a substrate. Knowing these properties suggests what an enzyme might do in the cell, Enzyme assays are laboratory procedures that measure the rate of enzyme reactions. Because enzymes are not consumed by the reactions they catalyse, enzyme assays usually follow changes in the concentration of substrates or products to measure the rate of reaction. There are many methods of measurement, spectrophotometric assays are most convenient since they allow the rate of the reaction to be measured continuously. Although radiometric assays require the removal and counting of samples they are extremely sensitive. An analogous approach is to use mass spectrometry to monitor the incorporation or release of stable isotopes as substrate is converted into product, the most sensitive enzyme assays use lasers focused through a microscope to observe changes in single enzyme molecules as they catalyse their reactions
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Transferase
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A transferase is any one of a class of enzymes that enact the transfer of specific functional groups from one molecule to another. They are involved in hundreds of different biochemical pathways throughout biology, transferases are involved in myriad reactions in the cell. Transferases are also utilized during translation, in this case, an amino acid chain is the functional group transferred by a peptidyl transferase. Group would be the group transferred as a result of transferase activity. The donor is often a coenzyme, some of the most important discoveries relating to transferases occurred as early as the 1930s. Earliest discoveries of transferase activity occurred in other classifications of enzymes, including Beta-galactosidase, protease, prior to the realization that individual enzymes were capable of such a task, it was believed that two or more enzymes enacted functional group transfers. This observance was later verified by the discovery of its reaction mechanism by Braunstein and their analysis showed that this reversible reaction could be applied to other tissues. This assertion was validated by Rudolf Schoenheimers work with radioisotopes as tracers in 1937 and this in turn would pave the way for the possibility that similar transfers were a primary means of producing most amino acids via amino transfer. Another such example of early research and later reclassification involved the discovery of uridyl transferase. In 1953, the enzyme UDP-glucose pyrophosphorylase was shown to be a transferase, when it was found that it could reversibly produce UTP and G1P from UDP-glucose, another example of historical significance relating to transferase is the discovery of the mechanism of catecholamine breakdown by catechol-O-methyltransferase. This discovery was a part of the reason for Julius Axelrod’s 1970 Nobel Prize in Physiology or Medicine. Classification of transferases continues to this day, with new ones being discovered frequently, an example of this is Pipe, a sulfotransferase involved in the dorsal-ventral patterning of Drosophilia. Initially, the mechanism of Pipe was unknown, due to a lack of information on its substrate. Research into Pipes catalytic activity eliminated the likelihood of it being a heparan sulfate glycosaminoglycan, further research has shown that Pipe targets the ovarian structures for sulfation. Pipe is currently classified as a Drosophilia heparan sulfate 2-O-sulfotransferase, systematic names of transferases are constructed in the form of donor, acceptor grouptransferase. For example, a DNA methyltransferase is a transferase that catalyzes the transfer of a group to a DNA acceptor. In practice, many molecules are not referred to using this terminology due to more prevalent common names, in the EC system of classification, the accepted name for RNA Polymerase is DNA-directed RNA polymerase. Described primarily based on the type of biochemical group transferred, transferases can be divided into ten categories and these categories comprise over 450 different unique enzymes
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Isomerase
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Isomerases are a general class of enzymes which convert a molecule from one isomer to another. Isomerases can either facilitate intramolecular rearrangements in which bonds are broken, the general form of such a reaction is as follows, A–B → B–A There is only one substrate yielding one product. This product has the molecular formula as the substrate but differs in bond connectivity or spatial arrangements. Isomerases catalyze reactions across many biological processes, such as in glycolysis, Isomerases catalyze changes within one molecule. They convert one isomer to another, meaning that the end product has the molecular formula. Isomers themselves exist in many varieties but can generally be classified as structural isomers or stereoisomers, structural isomers have a different ordering of bonds and/or different bond connectivity from one another, as in the case of hexane and its four other isomeric forms. Stereoisomers have the same ordering of bonds and the same connectivity. For example, 2-butene exists in two forms, cis-2-butene and trans-2-butene. The sub-categories of isomerases containing racemases, epimerases and cis-trans isomers are examples of enzymes catalyzing the interconversion of stereoisomers, intramolecular lyases, oxidoreductases and transferases catalyze the interconversion of structural isomers. The prevalence of each isomer in nature depends in part on the isomerization energy, isomers close in energy can interconvert easily and are often seen in comparable proportions. Isomerases can increase the rate by lowering the isomerization energy. Calculating isomerase kinetics from experimental data can be more difficult than for other enzymes because the use of product inhibition experiments is impractical, There are also practical difficulties in determining the rate-determining step at high concentrations in a single isomerization. Instead, tracer perturbation can overcome these technical difficulties if there are two forms of the unbound enzyme and this technique uses isotope exchange to measure indirectly the interconversion of the free enzyme between its two forms. The radiolabeled substrate and product diffuse in a time-dependent manner, when the system reaches equilibrium the addition of unlabeled substrate perturbs or unbalances it. As equilibrium is established again, the substrate and product are tracked to determine energetic information. This technique was adopted to study the profile of proline racemase. Generally, the names of isomerases are formed as substrate isomerase, enzyme-catalyzed reactions each have a uniquely assigned classification number. Isomerase-catalyzed reactions have their own EC category, EC5, Isomerases are further classified into six subclasses, This category includes and epimerases)
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