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Purine is a heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines and their tautomers. They are the most widely occurring nitrogen-containing heterocycles in nature.<ref>Template:Cite journal</ref>
Dietary sourcesEdit
Purines are found in high concentration in meat and meat products, especially internal organs, such as liver and kidney, and in various seafoods, high-fructose beverages, alcohol, and yeast products.<ref name="li">Template:Cite journal</ref><ref name="kaneko">Template:Cite journal</ref> Examples of high-purine food sources include anchovies, sardines, liver, beef, kidneys, brains, monkfish, dried mackerel, and shrimp.<ref name=kaneko/>
Foods particularly rich in hypoxanthine, adenine, and guanine lead to higher blood levels of uric acid.<ref name=kaneko/> Foods having more than 200 mg of hypoxanthine per 100 g, particularly animal and fish meats containing hypoxanthine as more than 50% of total purines, are more likely to increase uric acid levels.<ref name=kaneko/> Some vegetables, such as cauliflower, spinach, and peas, have considerable levels of purines, but do not contribute to elevated uric acid levels, possibily due to digestion and bioavailability factors.<ref name=kaneko/>
Dairy products, soy foods, cereals, beans, mushrooms, and coffee are low-purine foods, characterized specifically by low levels of adenine and guanine comprising more than 60% of purines.<ref name=kaneko/> A low-purine dietary plan that may reduce the risk of hyperuricemia and gout includes eggs, dairy products, fruits, vegetables, legumes, mushrooms, and soy products.<ref name=li/><ref name=kaneko/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
BiochemistryEdit
Purines and pyrimidines make up the two groups of nitrogenous bases, including the two groups of nucleotide bases. The purine bases are guanine (G) and adenine (A) which form corresponding nucleosides-deoxyribonucleosides (deoxyguanosine and deoxyadenosine) with deoxyribose moiety and ribonucleosides (guanosine, adenosine) with ribose moiety. These nucleosides with phosphoric acid form corresponding nucleotides (deoxyguanylate, deoxyadenylate and guanylate, adenylate) which are the building blocks of DNA and RNA, respectively. Purine bases also play an essential role in many metabolic and signalling processes within the compounds guanosine monophosphate (GMP) and adenosine monophosphate (AMP).
In order to perform these essential cellular processes, both purines and pyrimidines are needed by the cell, and in similar quantities. Both purine and pyrimidine are self-inhibiting and activating. When purines are formed, they inhibit the enzymes required for more purine formation. This self-inhibition occurs as they also activate the enzymes needed for pyrimidine formation. Pyrimidine simultaneously self-inhibits and activates purine in a similar manner. Because of this, there is nearly an equal amount of both substances in the cell at all times.<ref>Template:Cite book</ref>
PropertiesEdit
Purine is both a very weak acid (pKa 8.93) and an even weaker base (pKa 2.39).<ref>Template:Cite book</ref>
Purine is aromatic, having four tautomers each with a hydrogen bonded to a different one of the four nitrogen atoms. These are identified as 1-H, 3-H, 7-H, and 9-H (see image of numbered ring). The common crystalline form favours the 7-H tautomer, while in polar solvents both the 9-H and 7-H tautomers predominate.<ref>Template:Cite journal</ref> Substituents to the rings and interactions with other molecules can shift the equilibrium of these tautomers.<ref>Template:Cite journal</ref>
Notable purinesEdit
There are many naturally occurring purines. They include the nucleotide bases adenine and guanine. In DNA, these bases form hydrogen bonds with their complementary pyrimidines, thymine and cytosine, respectively. This is called complementary base pairing. In RNA, the complement of adenine is uracil instead of thymine.
Other notable purines are hypoxanthine, xanthine, theophylline, theobromine, caffeine, uric acid and isoguanine.
FunctionsEdit
Aside from the crucial roles of purines (adenine and guanine) in DNA and RNA, purines are also significant components in a number of other important biomolecules, such as ATP, GTP, cyclic AMP, NADH, and coenzyme A. Purine (1) itself, has not been found in nature, but it can be produced by organic synthesis.
They may also function directly as neurotransmitters, acting upon purinergic receptors. Adenosine activates adenosine receptors.
HistoryEdit
The word purine (pure urine)<ref name="McGuigan">Template:Cite book</ref> was coined by the German chemist Emil Fischer in 1884.<ref>Template:Cite journal Template:Open access
From p. 329 Template:Webarchive: "Um eine rationelle Nomenklatur der so entstehenden zahlreichen Substanzen zu ermöglichen, betrachte ich dieselben als Abkömmlinge der noch unbekannten Wasserstoffverbindung CH3.C5N4H3 and nenne die letztere Methylpurin." (In order to make possible a rational nomenclature for the numerous existing substances, I regarded them as derivatives of a still unknown hydrogen compound, CH3.C5N4H3, and call the latter "methylpurine".)</ref><ref name=Fischer1898>Template:Cite journal Template:Open access
From p. 2550 Template:Webarchive: "…hielt ich es für zweckmäßig, alle diese Produkte ebenso wie die Harnsäure als Derivate der sauerstofffreien Verbindung C5H4N4 zu betrachten, und wählte für diese den Namen Purin, welcher aus den Wörtern purum und uricum kombiniert war." (…I regarded it as expedient to consider all of these products, just like uric acid, as derivatives of the oxygen-free compound C5H4N4, and chose for them the name "purine", which was formed from the [Latin] words purum and uricum.)</ref> He synthesized it for the first time in 1898.<ref name=Fischer1898/> The starting material for the reaction sequence was uric acid (8), which had been isolated from kidney stones by Carl Wilhelm Scheele in 1776.<ref>Template:Cite journal</ref> Uric acid was reacted with PCl5 to give 2,6,8-trichloropurine, which was converted with HI and PH4I to give 2,6-diiodopurine. The product was reduced to purine using zinc dust.
- Template:Clear-leftFile:FischerPurineSynthesis-crop.svgConversion of uric acid (left) to purine (right) via 2,6,8-trichloropurine and 2,6-diiodopurine intermediates
MetabolismEdit
Template:Main article Many organisms have metabolic pathways to synthesize and break down purines.
Purines are biologically synthesized as nucleosides (bases attached to ribose).
Accumulation of modified purine nucleotides is defective to various cellular processes, especially those involving DNA and RNA. To be viable, organisms possess a number of deoxypurine phosphohydrolases, which hydrolyze these purine derivatives removing them from the active NTP and dNTP pools. Deamination of purine bases can result in accumulation of such nucleotides as ITP, dITP, XTP and dXTP.<ref name="pmid 22531138">Template:Cite journal</ref>
Defects in enzymes that control purine production and breakdown can severely alter a cell's DNA sequences, which may explain why people who carry certain genetic variants of purine metabolic enzymes have a higher risk for some types of cancer.
Purine biosynthesis in the three domains of lifeEdit
Organisms in all three domains of life, eukaryotes, bacteria and archaea, are able to carry out de novo biosynthesis of purines. This ability reflects the essentiality of purines for life. The biochemical pathway of synthesis is very similar in eukaryotes and bacterial species, but is more variable among archaeal species.<ref name="Brown2011">Template:Cite journal</ref> A nearly complete, or complete, set of genes required for purine biosynthesis was determined to be present in 58 of the 65 archaeal species studied.<ref name = Brown2011/> However, also identified were seven archaeal species with entirely, or nearly entirely, absent purine encoding genes. Apparently the archaeal species unable to synthesize purines are able to acquire exogenous purines for growth.,<ref name = Brown2011/> and are thus analogous to purine mutants of eukaryotes, e.g. purine mutants of the Ascomycete fungus Neurospora crassa,<ref>Template:Cite journal</ref> that also require exogenous purines for growth.
Laboratory synthesisEdit
In addition to in vivo synthesis of purines in purine metabolism, purine can also be synthesized artificially.
Purine is obtained in good yield when formamide is heated in an open vessel at 170 °C for 28 hours.<ref name="Yamada">Template:Cite journal</ref>
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This reaction and others like it have been discussed in the context of the origin of life.<ref name="Saladino">Template:Cite journal</ref>
Oro and Kamat (1961) and Orgel co-workers (1966, 1967) have shown that four molecules of HCN tetramerize to form diaminomaleodinitrile (12), which can be converted into almost all naturally occurring purines.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite book</ref> For example, five molecules of HCN condense in an exothermic reaction to make adenine, especially in the presence of ammonia.
Template:Anchor The Traube purine synthesis (1900) is a classic reaction (named after Wilhelm Traube) between an amine-substituted pyrimidine and formic acid.<ref>Template:Cite book</ref>
Prebiotic synthesis of purine ribonucleosidesEdit
In order to understand how life arose, knowledge is required of the chemical pathways that permit formation of the key building blocks of life under plausible prebiotic conditions. Nam et al. (2018)<ref>Template:Cite journal</ref> demonstrated the direct condensation of purine and pyrimidine nucleobases with ribose to give ribonucleosides in aqueous microdroplets, a key step leading to RNA formation. Also, a plausible prebiotic process for synthesizing purine ribonucleosides was presented by Becker et al. in 2016.<ref>Template:Cite journal</ref>
See alsoEdit
ReferencesEdit
Template:Reflist Template:Nucleobases, nucleosides, and nucleotides Template:Purinergics