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Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms. ==Biosynthesis== Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to ribose 5-phosphate. A key regulatory step is the production of 5-phospho-α-D-ribosyl 1-pyrophosphate (PRPP) by PRPP synthetase, which is activated by inorganic phosphate and inactivated by purine ribonucleotides. It is not the committed step to purine synthesis because PRPP is also used in pyrimidine synthesis and salvage pathways. The first committed step is the reaction of PRPP, glutamine and water to 5'-phosphoribosylamine (PRA), glutamate, and pyrophosphate - catalyzed by amidophosphoribosyltransferase, which is activated by PRPP and inhibited by AMP, GMP and IMP. PRPP + L-Glutamine + H2O → PRA + L-Glutamate + PPi In the second step react PRA, glycine and ATP to create GAR, ADP, and pyrophosphate - catalyzed by phosphoribosylamine—glycine ligase (GAR synthetase). Due to the chemical lability of PRA, which has a half-life of 38 seconds at PH 7.5 and 37 °C, researchers have suggested that the compound is channeled from amidophosphoribosyltransferase to GAR synthetase ''in vivo.'' PRA + Glicine + ATP → GAR + ADP + Pi The third is catalyzed by phosphoribosylglycinamide formyltransferase. GAR + fTHF → fGAR + THF The fourth is catalyzed by phosphoribosylformylglycinamidine synthase. fGAR + L-Glutamine + ATP → fGAM + L-Glutamate + ADP + Pi The fifth is catalyzed by AIR synthetase (FGAM cyclase). fGAM + ATP → AIR + ADP + Pi + H2O The sixth is catalyzed by phosphoribosylaminoimidazole carboxylase. AIR + CO2 → CAIR + 2H+ The seventh is catalyzed by phosphoribosylaminoimidazolesuccinocarboxamide synthase. CAIR + L-Aspartate + ATP → SAICAR + ADP + Pi The eight is catalyzed by adenylosuccinate lyase. SAICAR → AICAR + Fumarate The ninth is catalyzed by phosphoribosylaminoimidazolecarboxamide formyltransferase. AICAR + fTHF → FAICAR + THF The last step is catalyzed by Inosine monophosphate synthase. FAICAR → IMP + H2O In eucaryotes the second, third, and fifth step are catalyzed by trifunctional purine biosynthetic protein adenosine-3, which is encoded by the GART gene. Both ninth and tenth step are accomplished by a single protein named Bifunctional purine biosynthesis protein PURH, encoded by the ATIC gene. Both adenine and guanine are derived from the nucleotide inosine monophosphate (IMP), which is the first compound in the pathway to have a completely formed purine ring system. Inosine monophosphate is synthesized on a pre-existing ribose-phosphate through a complex pathway (as shown in the figure on the right). The source of the carbon and nitrogen atoms of the purine ring, 5 and 4 respectively, come from multiple sources. The amino acid glycine contributes all its carbon (2) and nitrogen (1) atoms, with additional nitrogen atoms from glutamine (2) and aspartic acid (1), and additional carbon atoms from formyl groups (2), which are transferred from the coenzyme tetrahydrofolate as 10-formyltetrahydrofolate, and a carbon atom from bicarbonate (1). Formyl groups build carbon-2 and carbon-8 in the purine ring system, which are the ones acting as bridges between two nitrogen atoms. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Purine metabolism」の詳細全文を読む スポンサード リンク
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