Adenine

Adenine /ˈædɪnɪn/ (A, Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its derivatives have a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate (ATP) and the cofactors nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD). It also has functions in protein synthesis and as a chemical component of DNA and RNA.[2] The shape of adenine is complementary to either thymine in DNA or uracil in RNA.

The adjacent image shows pure adenine, as an independent molecule. When connected into DNA, a covalent bond is formed between deoxyribose sugar and the bottom left nitrogen, so removing the hydrogen. The remaining structure is called an adenine residue, as part of a larger molecule. Adenosine is adenine reacted with ribose as used in RNA and ATP; deoxyadenosine, adenine attached to deoxyribose, as is used to form DNA.

Adenine
Adenine
Adenine-3D-balls
Adenine-3D-vdW
Names
IUPAC name
9H-purin-6-amine
Other names
6-aminopurine
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.724
EC Number 200-796-1
KEGG
RTECS number AU6125000
UNII
Properties
C5H5N5
Molar mass 135.13 g/mol
Appearance white to light yellow, crystalline
Density 1.6 g/cm3 (calculated)
Melting point 360 to 365 °C (680 to 689 °F; 633 to 638 K) decomposes
0.103 g/100 mL
Solubility negligible in ethanol
Acidity (pKa) 4.15 (secondary), 9.80 (primary)[1]
Thermochemistry
147.0 J/(K·mol)
96.9 kJ/mol
Hazards
Safety data sheet MSDS
Lethal dose or concentration (LD, LC):
227 mg/kg (rat, oral)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Structure

Adenine numbered
Adenine structure, with standard numbering of positions in red.

Adenine forms several tautomers, compounds that can be rapidly interconverted and are often considered equivalent. However, in isolated conditions, i.e. in an inert gas matrix and in the gas phase, mainly the 9H-adenine tautomer is found.[3][4]

Biosynthesis

Purine metabolism involves the formation of adenine and guanine. Both adenine and guanine are derived from the nucleotide inosine monophosphate (IMP), which in turn is synthesized from a pre-existing ribose phosphate through a complex pathway using atoms from the amino acids glycine, glutamine, and aspartic acid, as well as the coenzyme tetrahydrofolate.

Both adenine and guanine are derived from the nucleotide inosine monophosphate (IMP), a class of molecular structures which have evolved into nucleic acids, the information half of the duality of functions of nucleic acids, the other half being the atomic-molecular elements which biochemically and molecular/cellular biology form the dynamic and chaotic life bearing process of organic carbon based life forms. IMP is the "template" molecular structure for nucleotides, thus the molecular structure of extant nucleic acids.

Function

Adenine is one of the two purine nucleobases (the other being guanine) used in forming nucleotides of the nucleic acids. In DNA, adenine binds to thymine via two hydrogen bonds to assist in stabilizing the nucleic acid structures. In RNA, which is used for protein synthesis, adenine binds to uracil.

Base pair AT Base pair AU Base pair AD Base pair APsi
A-T-Base-pair (DNA) A-U-Base-pair (RNA) A-D-Base-pair (RNA) A-Ψ-Base-pair (RNA)

Adenine forms adenosine, a nucleoside, when attached to ribose, and deoxyadenosine when attached to deoxyribose. It forms adenosine triphosphate (ATP), a nucleoside triphosphate, when three phosphate groups are added to adenosine. Adenosine triphosphate is used in cellular metabolism as one of the basic methods of transferring chemical energy between chemical reactions.

Adenosin Desoxyadenosin
Adenosine, A Deoxyadenosine, dA

History

Template from Crick and Watson’s DNA molecular model, 1953. (9660573227)
Adenine on Crick and Watson's DNA molecular model, 1953. The picture is shown upside down compared to most modern drawings of adenine, such as those used in this article.

In older literature, adenine was sometimes called Vitamin B4.[5] Due to it being synthesized by the body and not essential to be obtained by diet, it does not meet the definition of vitamin and is no longer part of the Vitamin B complex. However, two B vitamins, niacin and riboflavin, bind with adenine to form the essential cofactors nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD), respectively. Hermann Emil Fischer was one of the early scientists to study adenine.

It was named in 1885 by Albrecht Kossel, in reference to the pancreas (a specific gland - in Greek, ἀδήν "aden") from which Kossel's sample had been extracted.[6][7]

Experiments performed in 1961 by Joan Oró have shown that a large quantity of adenine can be synthesized from the polymerization of ammonia with five hydrogen cyanide (HCN) molecules in aqueous solution;[8] whether this has implications for the origin of life on Earth is under debate.[9]

On August 8, 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting building blocks of DNA and RNA (adenine, guanine and related organic molecules) may have been formed extraterrestrially in outer space.[10][11][12] In 2011, physicists reported that adenine has an "unexpectedly variable range of ionization energies along its reaction pathways" which suggested that "understanding experimental data on how adenine survives exposure to UV light is much more complicated than previously thought"; these findings have implications for spectroscopic measurements of heterocyclic compounds, according to one report.[13]

Derivatives

  1. Nonapyrimine
  2. tubercidin
  3. Adenosine
  4. BWA78U

References

  1. ^ Dawson, R.M.C., et al., Data for Biochemical Research, Oxford, Clarendon Press, 1959.
  2. ^ Definition of Adenine from the Genetics Home Reference - National Institutes of Health
  3. ^ Plützer, Chr.; Kleinermanns, K. (2002). "Tautomers and electronic states of jet-cooled adenine investigated by double resonance spectroscopy". Phys. Chem. Chem. Phys. 4 (20): 4877–4882. Bibcode:2002PCCP....4.4877P. doi:10.1039/b204595h.
  4. ^ M. J. Nowak; H. Rostkowska; L. Lapinski; J. S. Kwiatkowski; J. Leszczynski (1994). "Experimental matrix isolation and theoretical ab initio HF/6-31G(d, p) studies of infrared spectra of purine, adenine and 2-chloroadenine,". Spectrochimica Acta Part A: Molecular Spectroscopy. 50 (6): 1081–1094. Bibcode:1994AcSpA..50.1081N. doi:10.1016/0584-8539(94)80030-8. ISSN 0584-8539.
  5. ^ Reader V (1930). "The assay of vitamin B(4)". The Biochemical Journal. 24 (6): 1827–31. doi:10.1042/bj0241827. PMC 1254803. PMID 16744538.
  6. ^ A. Kossel (1885) "Ueber eine neue Base aus dem Thierkörper" (On a new base from the animal body), Berichte der Deutschen Chemischen Gesellschaft zu Berlin, 18 : 79-81. From p. 79: "Diese Base, für welche ich den Namen Adenin vorschlage, wurde zunächst aus Pankreasdrüsen vom Rind dargestellt." (This base, for which I suggest the name "adenine", was first prepared from the pancreas glands of steer.)
  7. ^ Online Etymology Dictionary by Douglas Harper
  8. ^ Oro J, Kimball AP (August 1961). "Synthesis of purines under possible primitive earth conditions. I. Adenine from hydrogen cyanide". Archives of Biochemistry and Biophysics. 94 (2): 217–27. doi:10.1016/0003-9861(61)90033-9. PMID 13731263.
  9. ^ Shapiro, Robert (June 1995). "The prebiotic role of adenine: A critical analysis". Origins of Life and Evolution of Biospheres. 25 (1–3): 83–98. Bibcode:1995OLEB...25...83S. doi:10.1007/BF01581575.
  10. ^ Callahan MP, Smith KE, Cleaves HJ, Ruzicka J, Stern JC, Glavin DP, House CH, Dworkin JP (Aug 2011). "Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases". Proceedings of the National Academy of Sciences of the United States of America. 108 (34): 13995–8. Bibcode:2011PNAS..10813995C. doi:10.1073/pnas.1106493108. PMC 3161613. PMID 21836052.
  11. ^ Steigerwald, John (8 August 2011). "NASA Researchers: DNA Building Blocks Can Be Made in Space". NASA. Retrieved 2011-08-10.
  12. ^ ScienceDaily Staff (9 August 2011). "DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests". ScienceDaily. Retrieved 2011-08-09.
  13. ^ Williams P (August 18, 2011). "Physicists Uncover New Data On Adenine, a Crucial Building Block of Life". Science Daily. Retrieved 2011-09-01. journal reference: Mario Barbatti, Susanne Ullrich. Ionization potentials of adenine along the internal conversion pathways. Physical Chemistry Chemical Physics, 2011; doi:10.1039/C1CP21350D -- a University of Georgia physicist and a collaborator in Germany have shown that ... adenine, has an unexpectedly variable range of ionization energies along its reaction pathways....

External links

Adenine phosphoribosyltransferase

Adenine phosphoribosyltransferase (APRTase) is an enzyme encoded by the APRT gene, found in humans on chromosome 16. It is part of the Type I PRTase family and is involved in the nucleotide salvage pathway, which provides an alternative to nucleotide biosynthesis de novo in humans and most other animals. In parasitic protozoa such as giardia, APRTase provides the sole mechanism by which adenine can be produced. APRTase deficiency contributes to the formation of kidney stones (urolithiasis) and to potential kidney failure.

Adenine phosphoribosyltransferase deficiency

Adenine phosphoribosyltransferase deficiency (also called APRT deficiency or 2,8 dihydroxyadenine urolithiasis) is an autosomal recessive metabolic disorder associated with a mutation in the enzyme adenine phosphoribosyltransferase.

DNA methyltransferase

In biochemistry, the DNA methyltransferase (DNA MTase) family of enzymes catalyze the transfer of a methyl group to DNA. DNA methylation serves a wide variety of biological functions. All the known DNA methyltransferases use S-adenosyl methionine (SAM) as the methyl donor.

Deoxyribonuclease IV

Deoxyribonuclease IV (phage-T4-induced) (EC 3.1.21.2, endodeoxyribonuclease IV (phage T4-induced), E. coli endonuclease IV, endodeoxyribonuclease, redoxyendonuclease, deoxriboendonuclease, Escherichia coli endonuclease II, endonuclease II, DNA-adenine-transferase) is an enzyme. This enzyme catalyses the following chemical reaction

Endonucleolytic cleavage to 5'-phosphooligonucleotide end-productsDeoxyribonuclease IV is a type of deoxyribonuclease that functions at AP-sites.

Flavin adenine dinucleotide

In biochemistry, flavin adenine dinucleotide (FAD) is a redox-active coenzyme associated with various proteins, which is involved with several important enzymatic reactions in metabolism. A flavoprotein is a protein that contains a flavin group, this may be in the form of FAD or flavin mononucleotide (FMN). There are many flavoproteins besides components of the succinate dehydrogenase complex, including α-ketoglutarate dehydrogenase and a component of the pyruvate dehydrogenase complex; some examples are shown in section 6.

FAD can exist in four different redox states, which are the flavin-N(5)-oxide, quinone, semiquinone, and hydroquinone. FAD is converted between these states by accepting or donating electrons. FAD, in its fully oxidized form, or quinone form, accepts two electrons and two protons to become FADH2 (hydroquinone form). The semiquinone (FADH·) can be formed by either reduction of FAD or oxidation of FADH2 by accepting or donating one electron and one proton, respectively. Some proteins, however, generate and maintain a superoxidized form of the flavin cofactor, the flavin-N(5)-oxide.

Flavin mononucleotide

Flavin mononucleotide (FMN), or riboflavin-5′-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as prosthetic group of various oxidoreductases including NADH dehydrogenase as well as cofactor in biological blue-light photo receptors. During the catalytic cycle, a reversible interconversion of the oxidized (FMN), semiquinone (FMNH•) and reduced (FMNH2) forms occurs in the various oxidoreductases. FMN is a stronger oxidizing agent than NAD and is particularly useful because it can take part in both one- and two-electron transfers. In its role as blue-light photo receptor, (oxidized) FMN stands out from the 'conventional' photo receptors as the signaling state and not an E/Z isomerization.

It is the principal form in which riboflavin is found in cells and tissues. It requires more energy to produce, but is more soluble than riboflavin.

Guanine

Guanine (; or G, Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is called guanosine.

With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with conjugated double bonds. Being unsaturated, the bicyclic molecule is planar.

Hypoxanthine

Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids, where it is present in the anticodon of tRNA in the form of its nucleoside inosine. It has a tautomer known as 6-hydroxypurine. Hypoxanthine is a necessary additive in certain cell, bacteria, and parasite cultures as a substrate and nitrogen source. For example, it is commonly a required reagent in malaria parasite cultures, since Plasmodium falciparum requires a source of hypoxanthine for nucleic acid synthesis and energy metabolism.

In August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting hypoxanthine and related organic molecules, including the DNA and RNA components adenine and guanine, may have been formed extraterrestrially in outer space.The Pheretima aspergillum worm, used in Chinese medicine preparations, contains hypoxanthine.

MAS1

MAS proto-oncogene, or MAS1 proto-oncogene, G protein-coupled receptor (MRGA,MAS,MGRA""), is a protein that in humans is encoded by the MAS1 gene.

The structure of the MAS1 product indicates that it belongs to the class of receptors that are coupled to GTP-binding proteins and share a conserved structural motif, which is described as a '7-transmembrane segment' following the prediction that these hydrophobic segments form membrane-spanning alpha-helices. The MAS1 protein may be a receptor that, when activated, modulates a critical component in a growth-regulating pathway to bring about oncogenic effects.Agonists of the receptor include angiotensin-(1-7). Antagonist include A-779 (angiotensin-1-7 with c-terminal proline substituted for D-Ala), or D-Pro (angiotensin-1-7 with c-terminal proline submitted for D-proline).

Mas1 proto-oncogene (MAS1, MGRA) is not to be confused with the MAS-related G-protein coupled receptor, a recently believed to be activated by the ligand alamandine (generated by catalysis of Ang A via ACE2 or directly from Ang-(1-7)).

Nicotinamide adenine dinucleotide

Nicotinamide adenine dinucleotide (NAD) is a cofactor found in all living cells. The compound is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine nucleobase and the other nicotinamide. Nicotinamide adenine dinucleotide exists in two forms: an oxidized and reduced form abbreviated as NAD+ and NADH respectively.

In metabolism, nicotinamide adenine dinucleotide is involved in redox reactions, carrying electrons from one reaction to another. The cofactor is, therefore, found in two forms in cells: NAD+ is an oxidizing agent – it accepts electrons from other molecules and becomes reduced. This reaction forms NADH, which can then be used as a reducing agent to donate electrons. These electron transfer reactions are the main function of NAD. However, it is also used in other cellular processes, most notably a substrate of enzymes that add or remove chemical groups from proteins, in posttranslational modifications. Because of the importance of these functions, the enzymes involved in NAD metabolism are targets for drug discovery.

In organisms, NAD can be synthesized from simple building-blocks (de novo) from the amino acids tryptophan or aspartic acid. In an alternative fashion, more complex components of the coenzymes are taken up from food as niacin. Similar compounds are released by reactions that break down the structure of NAD. These preformed components then pass through a salvage pathway that recycles them back into the active form. Some NAD is converted into nicotinamide adenine dinucleotide phosphate (NADP); the chemistry of this related coenzyme is similar to that of NAD, but it has different roles in metabolism.

Although NAD+ is written with a superscript plus sign because of the formal charge on a particular nitrogen atom, at physiological pH for the most part it is actually a singly charged anion (charge of minus 1), while NADH is a doubly charged anion, because of the two bridging phosphate groups.

Nicotinamide adenine dinucleotide phosphate

Nicotinamide adenine dinucleotide phosphate, abbreviated NADP+ or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as lipid and nucleic acid synthesis, which require NADPH as a reducing agent.

NADPH is the reduced form of NADP+. NADP+ differs from NAD+ in the presence of an additional phosphate group on the 2' position of the ribose ring that carries the adenine moiety.

Nucleobase

Nucleobases, also known as nitrogenous bases or often simply bases, are nitrogen-containing biological compounds that form nucleosides, which in turn are components of nucleotides, with all of these monomers constituting the basic building blocks of nucleic acids. The ability of nucleobases to form base pairs and to stack one upon another leads directly to long-chain helical structures such as ribonucleic acid (RNA) and deoxyribonucleic acid (DNA).

Five nucleobases—adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U)—are called primary or canonical. They function as the fundamental units of the genetic code, with the bases A, G, C, and T being found in DNA while A, G, C, and U are found in RNA. Thymine and uracil are identical excepting that T includes a methyl group that U lacks.

Adenine and guanine have a fused-ring skeletal structure derived of purine, hence they are called purine bases. Similarly, the simple-ring structure of cytosine, uracil, and thymine is derived of pyrimidine, so those three bases are called the pyrimidine bases. Each of the base pairs in a typical double-helix DNA comprises a purine and a pyrimidine: either an A paired with a T or a C paired with a G. These purine-pyrimidine pairs, which are called base complements, connect the two strands of the helix and are often compared to the rungs of a ladder. The pairing of purines and pyrimidines may result, in part, from dimensional constraints, as this combination enables a geometry of constant width for the DNA spiral helix. The A-T and C-G pairings function to form double or triple hydrogen bonds between the amine and carbonyl groups on the complementary bases.

In August 2011, a report based on NASA studies of meteorites suggested that nucleobases such as adenine, guanine, xanthine, hypoxanthine, purine, 2,6-diaminopurine, and 6,8-diaminopurine may have formed in outer space as well as on earth.The origin of the term base reflects these compounds' chemical properties in acid-base reactions, but those properties are not especially important for understanding most of the biological functions of nucleobases.

Pentosyltransferase

Pentosyltransferases are a type of glycosyltransferase that catalyze the transfer of a pentose.

Examples include:

adenine phosphoribosyltransferase

hypoxanthine-guanine phosphoribosyltransferase

pertussis toxin

poly ADP ribose polymeraseThey are classified under EC number 2.4.2.

Polyadenylation

Polyadenylation is the addition of a poly(A) tail to a messenger RNA. The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In eukaryotes, polyadenylation is part of the process that produces mature messenger RNA (mRNA) for translation. It, therefore, forms part of the larger process of gene expression.

The process of polyadenylation begins as the transcription of a gene terminates. The 3'-most segment of the newly made pre-mRNA is first cleaved off by a set of proteins; these proteins then synthesize the poly(A) tail at the RNA's 3' end. In some genes these proteins add a poly(A) tail at one of several possible sites. Therefore, polyadenylation can produce more than one transcript from a single gene (alternative polyadenylation), similar to alternative splicing.The poly(A) tail is important for the nuclear export, translation, and stability of mRNA. The tail is shortened over time, and, when it is short enough, the mRNA is enzymatically degraded. However, in a few cell types, mRNAs with short poly(A) tails are stored for later activation by re-polyadenylation in the cytosol. In contrast, when polyadenylation occurs in bacteria, it promotes RNA degradation. This is also sometimes the case for eukaryotic non-coding RNAs.mRNA molecules in both prokaryotes and eukaryotes have polyadenylated 3'-ends, with the prokaryotic poly(A) tails generally shorter and less mRNA molecules polyadenylated.

Purine metabolism

Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.

SLC25A5

Solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator), member 5 is a protein that in humans is encoded by the SLC25A5 gene on the X chromosome.This protein functions as an antiporter for ADP/ATP exchange between the mitochondrial matrix and cytoplasm. As a result, it plays a key role in maintaining mitochondrial membrane potential and inhibiting apoptosis and has been targeted for treating cancer.

Thymine

Thymine (T, Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. In RNA, thymine is replaced by the nucleobase uracil. Thymine was first isolated in 1893 by Albrecht Kossel and Albert Neumann from calves' thymus glands, hence its name.

Uracil

Uracil (; U) is one of the four nucleobases in the nucleic acid of RNA that are represented by the letters A, G, C and U. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by thymine. Uracil is a demethylated form of thymine.

Uracil is a common and naturally occurring pyrimidine derivative. The name "uracil" was coined in 1885 by the German chemist Robert Behrend, who was attempting to synthesize derivatives of uric acid. Originally discovered in 1900 by Alberto Ascoli, it was isolated by hydrolysis of yeast nuclein; it was also found in bovine thymus and spleen, herring sperm, and wheat germ. It is a planar, unsaturated compound that has the ability to absorb light.Based on 12C/13C isotopic ratios of organic compounds found in the Murchison meteorite, it is believed that uracil, xanthine and related molecules can also be formed extraterrestrially.In 2012, an analysis of data from the Cassini mission orbiting in the Saturn system showed that Titan's surface composition may include uracil.

Vidarabine

Vidarabine or 9-β-D-arabinofuranosyladenine (ara-A) is an antiviral drug which is active against herpes simplex and varicella zoster viruses.

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