Nucleotides are organic molecules that serve as the monomer units for forming the nucleic acid polymers deoxyribonucleic acid and ribonucleic acid, both of which are essential biomolecules within all life-forms on Earth. Nucleotides are the building blocks of nucleic acids. A nucleoside is a 5-carbon sugar, thus a nucleoside plus a phosphate group yields a nucleotide. Nucleotides play a central role in metabolism at a fundamental, cellular level, they carry packets of chemical energy—in the form of the nucleoside triphosphates Adenosine triphosphate, Guanosine triphosphate, Cytidine triphosphate and Uridine triphosphate —throughout the cell to the many cellular functions that demand energy, which include: synthesizing amino acids and cell membranes and parts, moving the cell and moving cell parts, dividing the cell, etc. In addition, nucleotides participate in cell signaling, are incorporated into important cofactors of enzymatic reactions. In experimental biochemistry, nucleotides can be radiolabeled with radionuclides to yield radionucleotides.
A nucleotide is composed of three distinctive chemical sub-units: a five-carbon sugar molecule, a nitrogenous base—which two together are called a nucleoside—and one phosphate group. With all three joined, a nucleotide is termed a "nucleoside monophosphate"; the chemistry sources ACS Style Guide and IUPAC Gold Book prescribe that a nucleotide should contain only one phosphate group, but common usage in molecular biology textbooks extends the definition to include molecules with two, or with three, phosphates. Thus, the terms "nucleoside diphosphate" or "nucleoside triphosphate" may indicate nucleotides. Nucleotides contain either a purine or a pyrimidine base—i.e. The nitrogenous base molecule known as a nucleobase—and are termed ribonucleotides if the sugar is ribose, or deoxyribonucleotides if the sugar is deoxyribose. Individual phosphate molecules repetitively connect the sugar-ring molecules in two adjacent nucleotide monomers, thereby connecting the nucleotide monomers of a nucleic acid end-to-end into a long chain.
These chain-joins of sugar and phosphate molecules create a'backbone' strand for a single- or double helix. In any one strand, the chemical orientation of the chain-joins runs from the 5'-end to the 3'-end —referring to the five carbon sites on sugar molecules in adjacent nucleotides. In a double helix, the two strands are oriented in opposite directions, which permits base pairing and complementarity between the base-pairs, all, essential for replicating or transcribing the encoded information found in DNA. Unlike in nucleic acid nucleotides, singular cyclic nucleotides are formed when the phosphate group is bound twice to the same sugar molecule, i.e. at the corners of the sugar hydroxyl groups. These individual nucleotides function in cell metabolism rather than the nucleic acid structures of long-chain molecules. Nucleic acids are polymeric macromolecules assembled from nucleotides, the monomer-units of nucleic acids; the purine bases adenine and guanine and pyrimidine base cytosine occur in both DNA and RNA, while the pyrimidine bases thymine and uracil in just one.
Adenine forms a base pair with thymine with two hydrogen bonds, while guanine pairs with cytosine with three hydrogen bonds. Nucleotides can be synthesized by a variety of means both in vitro and in vivo. In vitro, protecting groups may be used during laboratory production of nucleotides. A purified nucleoside is protected to create a phosphoramidite, which can be used to obtain analogues not found in nature and/or to synthesize an oligonucleotide. In vivo, nucleotides can be recycled through salvage pathways; the components used in de novo nucleotide synthesis are derived from biosynthetic precursors of carbohydrate and amino acid metabolism, from ammonia and carbon dioxide. The liver is the major organ of de novo synthesis of all four nucleotides. De novo synthesis of pyrimidines and purines follows two different pathways. Pyrimidines are synthesized first from aspartate and carbamoyl-phosphate in the cytoplasm to the common precursor ring structure orotic acid, onto which a phosphorylated ribosyl unit is covalently linked.
Purines, are first synthesized from the sugar template onto which the ring synthesis occurs. For reference, the syntheses of the purine and pyrimidine nucleotides are carried out by several enzymes in the cytoplasm of the cell, not within a specific organelle. Nucleotides undergo breakdown such that useful parts can be reused in synthesis reactions to create new nucleotides; the synthesis of the pyrimidines CTP and UTP occurs in the cytoplasm and starts with the formation of carbamoyl phosphate from glutamine and CO2. Next, aspartate carbamoyltransferase catalyzes a condensation reaction between aspartate and carbamoyl phosphate to form carbamoyl aspartic acid, cyclized into 4,5-dihydroorotic acid by dihydroorotase; the latter is converted to orotate by dihydroorotate oxidase. The net reaction is: -Dihydroorotate + O2 → Orotate + H2O2Orotate is covalently linked with a phosphorylated ribosyl unit; the covalent linkage between the ribose and pyrimidine occurs at position C1 of the ribose unit, which contains a pyrophosphate, N1 of the pyrimidine ring.
Orotate phosphoribosyltransferase catalyzes the net reaction yielding orotidine monophosphate: Or
Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development and reproduction of all known organisms and many viruses. DNA and ribonucleic acid are nucleic acids; the two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases, a sugar called deoxyribose, 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 separate polynucleotide strands are bound together, according to base pairing rules, with hydrogen bonds to make double-stranded DNA; the complementary nitrogenous bases are divided into two groups and purines. In DNA, the pyrimidines are cytosine. Both strands of double-stranded DNA store the same biological information.
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 are thus antiparallel. Attached to each sugar is one of four types of nucleobases, it is the sequence of these four nucleobases along the backbone. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation. Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms store most of their DNA inside the cell nucleus as nuclear DNA, some in the mitochondria as mitochondrial DNA, or in chloroplasts as chloroplast DNA. In contrast, prokaryotes store their DNA only in circular chromosomes.
Within eukaryotic chromosomes, chromatin proteins, such as histones and organize DNA. These compacting 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, its molecular structure was first identified by Francis Crick and James Watson at the Cavendish Laboratory within the University of Cambridge in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Raymond Gosling, a post-graduate student of Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity; the unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials. DNA is a long polymer made from repeating units called nucleotides.
The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, have the same pitch of 34 angstroms; the pair of chains has a radius of 10 angstroms. According to another study, when measured in a different solution, the DNA chain measured 22 to 26 angstroms wide, one nucleotide unit measured 3.3 Å long. Although each individual nucleotide is small, a DNA polymer can be large and contain hundreds of millions, such as in chromosome 1. Chromosome 1 is the largest human chromosome with 220 million base pairs, would be 85 mm long if straightened. DNA does not exist as a single strand, but instead as a pair of strands that are held together; these two long strands coil in the shape of a double helix. The nucleotide contains both a segment of the backbone of a nucleobase. A nucleobase linked to a sugar is called a nucleoside, a base linked to a sugar and to one or more phosphate groups is called a nucleotide.
A biopolymer comprising multiple linked nucleotides is called a polynucleotide. The backbone of the DNA strand is made from alternating sugar residues; the sugar in DNA is 2-deoxyribose, a pentose sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings; these are known as the 3′-end, 5′-end carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond. When imagining DNA, each phosphoryl is considered to "belong" to the nucleotide whose 5′ carbon forms a bond therewith. Any DNA strand therefore has one end at which there is a phosphoryl attached to the 5′ carbon of a ribose and another end a
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
In chemistry, phosphorylation of a molecule is the attachment of a phosphoryl group. Together with its counterpart, dephosphorylation, it is critical for many cellular processes in biology. Phosphorylation is important for protein function. Many proteins are phosphorylated temporarily, as are many sugars and other molecules. Protein phosphorylation is considered the most abundant post-translational modification in eukaryotes. Phosphorylation can occur on serine and tyrosine side chains through phosphoester bond formation, on histidine and arginine through phosphoramidate bonds, on aspartic acid and glutamic acid through mixed anhydride linkages. Recent evidence confirms widespread histidine phosphorylation at both the 1 and 3 N-atoms of the imidazole ring Recent work from 2017 suggests widespread human protein phosphorylation on multiple non-canonical amino acids, including motifs containing phosphorylated histidine, glutamate and lysine in HeLa cell extracts. Due to the chemical lability of these phosphorylated residues, in marked contrast to Ser and Tyr phosphorylation, the analysis of phosphorylated histidine using standard biochemical and mass spectrometric approaches is much more challenging and special procedures and separation techniques are required for their preservation alongside classical Ser and Tyr phosphorylation.
The prominent role of protein phosphorylation in biochemistry is illustrated by the huge body of studies published on the subject. Phosphorylation of sugars is the first stage in their catabolism. Phosphorylation allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter. Phosphorylation of glucose is a key reaction in sugar metabolism because many sugars are first converted to glucose before they are metabolized further; the chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of glycolysis is given by D-glucose + ATP → D-glucose-6-phosphate + ADPΔG° = −16.7 kJ/mol Researcher D. G. Walker of the University of Birmingham determined the presence of two specific enzymes in adult guinea pig liver, both of which catalyze the phosphorylation of glucose to glucose 6 phosphate; the two enzymes have been identified as a specific non-specific hexokinase. Hepatic cell is permeable to glucose, the initial rate of phosphorylation of glucose is the rate-limiting step in glucose metabolism by the liver and non-specific hexokinase.
The role of glucose 6-phosphate in glycogen synthase: High blood glucose concentration causes an increase in intracellular levels of glucose 6 phosphate in liver, skeletal muscle and fat tissue. And non-specific hexokinase. In liver, synthesis of glycogen is directly correlated by blood glucose concentration and in skeletal muscle and adipocytes, glucose has a minor effect on glycogen synthase. High blood glucose releases insulin, stimulating the trans location of specific glucose transporters to the cell membrane; the liver’s crucial role in controlling blood sugar concentrations by breaking down glucose into carbon dioxide and glycogen is characterized by the negative delta G value, which indicates that this is a point of regulation with. The hexokinase enzyme has a low Km, indicating a high affinity for glucose, so this initial phosphorylation can proceed when glucose levels at nanoscopic scale within the blood; the phosphorylation of glucose can be enhanced by the binding of Fructose-6-phosphate, lessened by the binding fructose-1-phosphate.
Fructose consumed in the diet is converted to F1P in the liver. This negates the action of F6P on glucokinase, which favors the forward reaction; the capacity of liver cells to phosphorylate fructose exceeds capacity to metabolize fructose-1-phosphate. Consuming excess fructose results in an imbalance in liver metabolism, which indirectly exhausts the liver cell’s supply of ATP. Allosteric activation by glucose 6 phosphate, which acts as an effector, stimulates glycogen synthase, glucose 6 phosphate may inhibit the phosphorylation of glycogen synthase by cyclic AMP-stimulated protein kinase. Phosphorylation of glucose is imperative in processes within the body. For example, phosphorylating glucose is necessary for insulin-dependent mechanistic target of rapamycin pathway activity within the heart; this further suggests a link between cardiac growth. Reversible phosphorylation of proteins is an important regulatory mechanism that occurs in both prokaryotic and eukaryotic organisms, it is estimated that 230,000, 156,000 and 40,000 phosphorylation sites exist in human and yeast, respectively.
Kinases phosphorylate proteins and phosphatases dephosphorylate proteins. Many enzymes and receptors "off" by phosphorylation and dephosphorylation. Reversible phosphorylation results in a conformational change in the structure in many enzymes and receptors, causing them to become activated or deactivated. Phosphorylation occurs on serine, threonine and histidine residues in eukaryotic proteins. Histidine phosphorylation of eukaryotic proteins appears to be much more frequent than tyrosine phos
Nucleic acids are the biopolymers, or small biomolecules, essential to all known forms of life. The term nucleic acid is the overall name for DNA and RNA, they are composed of nucleotides, which are the monomers made of three components: a 5-carbon sugar, a phosphate group and a nitrogenous base. If the sugar is a compound ribose, the polymer is RNA. Nucleic acids are the most important of all biomolecules, they are found in abundance in all living things, where they function to create and encode and store information in the nucleus of every living cell of every life-form organism on Earth. In turn, they function to transmit and express that information inside and outside the cell nucleus—to the interior operations of the cell and to the next generation of each living organism; the encoded information is contained and conveyed via the nucleic acid sequence, which provides the'ladder-step' ordering of nucleotides within the molecules of RNA and DNA. Strings of nucleotides are bonded to form helical backbones—typically, one for RNA, two for DNA—and assembled into chains of base-pairs selected from the five primary, or canonical, which are: adenine, guanine and uracil.
Using amino acids and the process known as protein synthesis, the specific sequencing in DNA of these nucleobase-pairs enables storing and transmitting coded instructions as genes. In RNA, base-pair sequencing provides for manufacturing new proteins that determine the frames and parts and most chemical processes of all life forms. Nuclein were discovered by Friedrich Miescher in 1869. In the early 1880s Albrecht Kossel further purifies the substance and discovers its acidic properties, he also identifies the nucleobases. In 1889 Richard Altmann creates the term nucleic acid In 1938 Astbury and Bell published the first X-ray diffraction pattern of DNA. In 1953 Watson and Crick determined the structure of DNA. Experimental studies of nucleic acids constitute a major part of modern biological and medical research, form a foundation for genome and forensic science, the biotechnology and pharmaceutical industries; the term nucleic acid is the overall name for DNA and RNA, members of a family of biopolymers, is synonymous with polynucleotide.
Nucleic acids were named for their initial discovery within the nucleus, for the presence of phosphate groups. Although first discovered within the nucleus of eukaryotic cells, nucleic acids are now known to be found in all life forms including within bacteria, mitochondria, chloroplasts and viroids.. All living cells contain both DNA and RNA, while viruses contain either DNA or RNA, but not both; the basic component of biological nucleic acids is the nucleotide, each of which contains a pentose sugar, a phosphate group, a nucleobase. Nucleic acids are generated within the laboratory, through the use of enzymes and by solid-phase chemical synthesis; the chemical methods enable the generation of altered nucleic acids that are not found in nature, for example peptide nucleic acids. Nucleic acids are very large molecules. Indeed, DNA molecules are the largest individual molecules known. Well-studied biological nucleic acid molecules range in size from 21 nucleotides to large chromosomes. In most cases occurring DNA molecules are double-stranded and RNA molecules are single-stranded.
There are numerous exceptions, however—some viruses have genomes made of double-stranded RNA and other viruses have single-stranded DNA genomes, and, in some circumstances, nucleic acid structures with three or four strands can form. Nucleic acids are linear polymers of nucleotides; each nucleotide consists of three components: a purine or pyrimidine nucleobase, a pentose sugar, a phosphate group. The substructure consisting of a nucleobase plus sugar is termed a nucleoside. Nucleic acid types differ in the structure of the sugar in their nucleotides–DNA contains 2'-deoxyribose while RNA contains ribose; the nucleobases found in the two nucleic acid types are different: adenine and guanine are found in both RNA and DNA, while thymine occurs in DNA and uracil occurs in RNA. The sugars and phosphates in nucleic acids are connected to each other in an alternating chain through phosphodiester linkages. In conventional nomenclature, the carbons to which the phosphate groups attach are the 3'-end and the 5'-end carbons of the sugar.
This gives nucleic acids directionality, the ends of nucleic acid molecules are referred to as 5'-end and 3'-end. The nucleobases are joined to the sugars via an N-glycosidic linkage involving a nucleobase ring nitrogen and the 1' carbon of the pentose sugar ring. Non-standard nucleosides are found in both RNA and DNA and arise from modification of the standard nucleosides within the DNA molecule or the primary RNA transcript. Transfer RNA molecules contain a large number of modified nucleosides. Double-stranded nucleic acids are made up of complementary sequences, in which extensive Watson-Crick base pairing results in a repeated and quite uniform double-helical three-dimensional structure. In contrast, single-stranded
A hydroxy or hydroxyl group is the entity with the formula OH. It contains oxygen bonded to hydrogen. In organic chemistry and carboxylic acids contain hydroxy groups; the anion, called hydroxide, consists of a hydroxyl group. According to IUPAC rules, the term hydroxyl refers to the radical OH only, while the functional group −OH is called hydroxy group. Water, carboxylic acids, many other hydroxy-containing compounds can be deprotonated readily; this behavior is rationalized by the disparate electronegativities of hydrogen. Hydroxy-containing compounds engage in hydrogen bonding, which causes them to stick together, leading to higher boiling and melting points than found for compounds that lack this functional group. Organic compounds, which are poorly soluble in water, become water-soluble when they contain two or more hydroxy groups, as illustrated by sugars and amino acid; the hydroxy group is pervasive in biochemistry. Many inorganic compounds contain hydroxy groups, including sulfuric acid, the chemical compound produced on the largest scale industrially.
Hydroxy groups participate in the dehydration reactions that link simple biological molecules into long chains. The joining of a fatty acid to glycerol to form a triacylglycerol removes the −OH from the carboxy end of the fatty acid; the joining of two aldehyde sugars to form a disaccharide removes the −OH from the carboxy group at the aldehyde end of one sugar. The creation of a peptide bond to link two amino acids to make a protein removes the −OH from the carboxy group of one amino acid. Hydroxyl radicals are reactive and undergo chemical reactions that make them short-lived; when biological systems are exposed to hydroxyl radicals, they can cause damage to cells, including those in humans, where they can react with DNA, proteins. In 2009, India's Chandrayaan-1 satellite, NASA's Cassini spacecraft and the Deep Impact probe have each detected the presence of water by evidence of hydroxyl fragments on the Moon; as reported by Richard Kerr, "A spectrometer detected an infrared absorption at a wavelength of 3.0 micrometers that only water or hydroxyl—a hydrogen and an oxygen bound together—could have created."
NASA reported in 2009 that the LCROSS probe revealed an ultraviolet emission spectrum consistent with hydroxyl presence. The Venus Express orbiter sent back Venus science data from April 2006 until December 2014. Results from Venus Express include the detection of hydroxyl in the atmosphere. Hydronium Ion Oxide Reece, Jane. "Unit 1, Chapter 4 &5." In Campbell Biology. Berge, Susan. San Francisco: Pearson Benjamin Cummings. ISBN 978-0-321-55823-7
European Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation and Restriction of Chemicals. ECHA is the driving force among regulatory authorities in implementing the EU's chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and addresses chemicals of concern, it is located in Finland. The agency headed by Executive Director Bjorn Hansen, started working on 1 June 2007; the REACH Regulation requires companies to provide information on the hazards and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most used substances have been registered; the information is technical but gives detail on the impact of each chemical on people and the environment.
This gives European consumers the right to ask retailers whether the goods they buy contain dangerous substances. The Classification and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU; this worldwide system makes it easier for workers and consumers to know the effects of chemicals and how to use products safely because the labels on products are now the same throughout the world. Companies need to notify ECHA of the labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100 000 substances; the information is available on their website. Consumers can check chemicals in the products. Biocidal products include, for example, insect disinfectants used in hospitals; the Biocidal Products Regulation ensures that there is enough information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation; the law on Prior Informed Consent sets guidelines for the import of hazardous chemicals.
Through this mechanism, countries due to receive hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have serious effects on human health and the environment are identified as Substances of Very High Concern 1; these are substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment and do not break down. Other substances considered. Companies manufacturing or importing articles containing these substances in a concentration above 0,1% weight of the article, have legal obligations, they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy. Once a substance has been identified in the EU as being of high concern, it will be added to a list; this list is available on ECHA's website and shows consumers and industry which chemicals are identified as SVHCs.
Substances placed on the Candidate List can move to another list. This means that, after a given date, companies will not be allowed to place the substance on the market or to use it, unless they have been given prior authorisation to do so by ECHA. One of the main aims of this listing process is to phase out SVHCs where possible. In its 2018 substance evaluation progress report, ECHA said chemical companies failed to provide “important safety information” in nearly three quarters of cases checked that year. "The numbers show a similar picture to previous years" the report said. The agency noted that member states need to develop risk management measures to control unsafe commercial use of chemicals in 71% of the substances checked. Executive Director Bjorn Hansen called non-compliance with REACH a "worry". Industry group CEFIC acknowledged the problem; the European Environmental Bureau called for faster enforcement to minimise chemical exposure. European Chemicals Bureau Official website