In order to perform these essential cellular processes, both purines and pyrimidines are needed by thecell, and in similar quantities. Both purine and pyrimidine are self-inhibiting andactivating. When purines are formed, theyinhibit theenzymes 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.[5]
Purine is both a very weak acid (pKa 8.93) and an even weaker base (pKa 2.39).[6] If dissolved in pure water, thepH is halfway between these two pKa values.
Purine isaromatic, having fourtautomers 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.[7] Substituents to the rings and interactions with other molecules can shift the equilibrium of these tautomers.[8]
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 asATP,GTP,cyclic AMP,NADH, andcoenzyme A. Purine (1) itself, has not been found in nature, but it can be produced byorganic synthesis.
The wordpurine (pure urine)[9] was coined by theGermanchemistEmil Fischer in 1884.[10][11] He synthesized it for the first time in 1898.[11] The starting material for the reaction sequence wasuric acid (8), which had been isolated fromkidney stones byCarl Wilhelm Scheele in 1776.[12] Uric acid was reacted withPCl5 to give 2,6,8-trichloropurine, which was converted withHI andPH4I to give 2,6-diiodopurine. The product was reduced to purine usingzinc dust.
Conversion of uric acid (left) to purine (right) via 2,6,8-trichloropurine and 2,6-diiodopurine intermediates
Many organisms havemetabolic pathways to synthesize and break down purines.
Purines are biologically synthesized asnucleosides (bases attached toribose).
Accumulation of modified purine nucleotides is defective to various cellular processes, especially those involvingDNA andRNA. To be viable, organisms possess a number of deoxypurine phosphohydrolases, whichhydrolyze these purine derivatives removing them from the activeNTP anddNTP pools. Deamination of purine bases can result in accumulation of such nucleotides asITP,dITP,XTP anddXTP.[13]
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 ofcancer.
Organisms in all three domains of life,eukaryotes,bacteria andarchaea, are able to carry outde novobiosynthesis 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.[14] 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.[14] 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.,[14] and are thus analogous to purine mutants of eukaryotes, e.g. purine mutants of the Ascomycete fungusNeurospora crassa,[15] that also require exogenous purines for growth.
Higher levels ofmeat andseafood consumption are associated with an increased risk ofgout, whereas a higher level of consumption ofdairy products is associated with a decreased risk. Moderate intake of purine-rich vegetables or protein is not associated with an increased risk of gout.[16] Similar results have been found with the risk ofhyperuricemia.
In addition toin vivo synthesis of purines inpurine metabolism, purine can also be synthesized artificially.
Purine is obtained in good yield whenformamide is heated in an open vessel at 170 °C for 28 hours.[17]
This remarkable reaction and others like it have been discussed in the context ofthe origin of life.[18]
Patented August 20, 1968, the current recognized method of industrial-scale production of adenine is a modified form of the formamide method. This method heats up formamide under 120 °C conditions within a sealed flask for 5 hours to form adenine. The reaction is heavily increased in quantity by using a phosphorus oxychloride (phosphoryl chloride) or phosphorus pentachloride as an acid catalyst and sunlight or ultraviolet conditions. After the 5 hours have passed and the formamide-phosphorus oxychloride-adenine solution cools down, water is put into the flask containing the formamide and now-formed adenine. The water-formamide-adenine solution is then poured through a filtering column of activated charcoal. The water and formamide molecules, being small molecules, will pass through the charcoal and into the waste flask; the large adenine molecules, however, will attach or “adsorb” to the charcoal due to the van der waals forces that interact between the adenine and the carbon in the charcoal. Because charcoal has a large surface area, it's able to capture the majority of molecules that pass a certain size (greater than water and formamide) through it. To extract the adenine from the charcoal-adsorbed adenine, ammonia gas dissolved in water (aqua ammonia) is poured onto the activated charcoal-adenine structure to liberate the adenine into the ammonia-water solution. The solution containing water, ammonia, and adenine is then left to air dry, with the adenine losing solubility due to the loss of ammonia gas that previously made the solution basic and capable of dissolving adenine, thus causing it to crystallize into a pure white powder that can be stored.[19]
Oro and Kamat (1961) and Orgel co-workers (1966, 1967) have shown that four molecules ofHCN tetramerize to formdiaminomaleodinitrile (12), which can be converted into almost all naturally occurring purines.[20][21][22][23][24] For example, five molecules of HCN condense in an exothermic reaction to makeadenine, especially in the presence of ammonia.
In order to understand howlife arose, knowledge is required of the chemical pathways that permit formation of the key building blocks of life under plausibleprebiotic conditions. Nam et al. (2018)[26] 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 Beckeret al. in 2016.[27]
^Seela F, et al. (2014). "Hetarenes III (Six-Membered Rings and Larger Hetero-Rings with Maximum Unsaturation) — Part 2b". In Schaumann E (ed.).Houben-Weyl Methods of Organic Chemistry. Vol. E 9b/2 (4th Supplement ed.). Thieme. p. 310.ISBN978-3-13-181504-0.Archived from the original on 2022-02-17. Retrieved2020-05-15.
^Stasyuk OA, Szatyłowicz H, Krygowski TM (April 2012). "Effect of the H-bonding on aromaticity of purine tautomers".The Journal of Organic Chemistry.77 (8):4035–45.doi:10.1021/jo300406r.PMID22448684.
^Fischer E (1884)."Ueber die Harnsäure. I." [On uric acid. I.](PDF).Berichte der Deutschen Chemischen Gesellschaft.17:328–338.doi:10.1002/cber.18840170196. Retrieved2016-04-20. From p. 329Archived 2022-02-17 at theWayback Machine:"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".)
^abFischer E (1898)."Ueber das Purin und seine Methylderivate" [On purine and its methyl derivatives](PDF).Berichte der Deutschen Chemischen Gesellschaft.31 (3):2550–74.doi:10.1002/cber.18980310304. Retrieved2016-04-20. From p. 2550Archived 2020-10-18 at theWayback Machine:"…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] wordspurum anduricum.)
^Scheele CW (1776). "Examen chemicum calculi urinari" [A chemical examination of kidney stones].Opuscula.2: 73.
^Saladino R, Crestini C, Ciciriello F, Costanzo G, Di Mauro E (December 2006). "About a formamide-based origin of informational polymers: syntheses of nucleobases and favourable thermodynamic niches for early polymers".Origins of Life and Evolution of the Biosphere.36 (5–6):523–531.Bibcode:2006OLEB...36..523S.doi:10.1007/s11084-006-9053-2.PMID17136429.S2CID36278915.
^Sanchez RA, Ferris JP, Orgel LE (December 1967). "Studies in prebiotic synthesis. II. Synthesis of purine precursors and amino acids from aqueous hydrogen cyanide".Journal of Molecular Biology.30 (2):223–253.doi:10.1016/S0022-2836(67)80037-8.PMID4297187.
^Ferris JP, Orgel LE (March 1966). "An Unusual Photochemical Rearrangement in the Synthesis of Adenine from Hydrogen Cyanide".Journal of the American Chemical Society.88 (5): 1074.doi:10.1021/ja00957a050.
