Phosphoribosyl adenosine triphosphate

Recently, the formation of a covalent glycosyl-enzyme intermediate was also shown by Bell and Koshland (17) in another reaction. Evidence was presented that the mechanism of the enzyme, phosphoribosyl-adeno-sine triphosphate pyrophosphate phosphoribosyl transferase, proceeds through a covalent phosphoribosyl-enzyme intermediate. The intermediate has been demonstrated after incubating the enzyme with 14C-5-phosphoribosyl-l-pyrophosphate (PRPP) under native and denaturing conditions. The intermediate also forms from the reverse direction as shown when the enzyme is mixed with its product N- (5-phosphoribosyl-adenosine triphosphate (PR-ATP). These data give evidence for a covalent enzyme-substrate intermediate. The enzyme which catalyzes the overall reaction proceeds as follows ... 

Histidine 44 Cyclase Phosphoribosyl-adenosine triphosphate-pyro-phosphorylase ... 

The first reaction in His biosynthesis involves the transfer of N-1 and C-2 of the adenine moiety of ATP to the ribose phosphate unit of 5-phosphoribosyl-1 -pyrophosp hate (PRPP) (Figure 5.82). The key intermediate PRPP is condensed by the N -5 -phosphoribosyl-adenosine triphosphate (PRATP) transferase (encoded by gene... 

The first step of this sequence, which is not unique to de novo purine nucleotide biosynthesis, is the synthesis of 5-phosphoribosylpyrophosphate (PRPP) from ribose-5-phosphate and adenosine triphosphate. Phosphoribosyl-pyrophosphate synthetase, the enzyme that catalyses this reaction [278], is under feedback control by adenosine triphosphate [279]. Cordycepin interferes with thede novo pathway [229, 280, 281), and cordycepin triphosphate inhibits the synthesis of PRPP in extracts from Ehrlich ascites tumour cells [282]. Formycin [283], probably as the triphosphate, 9-0-D-xylofuranosyladenine [157] triphosphate, and decoyinine (LXXlll) [284-286] (p. 89) also inhibit the synthesis of PRPP in tumour cells, and this is held to be the blockade most important to their cytotoxic action. It has been suggested but not established that tubercidin (triphosphate) may also be an inhibitor of this reaction [193]. 

M15. Murray, A. W., and Wong, P. C. L., Stimulation of adenine Phosphoribosyl-transferase by adenosine triphosphate and other nucleoside triphosphates. Biochem. J. 104, 669 (1967). 

AMP, ADP, and ATP = adenosine mono-, di-, and triphosphate IMP = inosine 5 -monophosphate AICAR = 5 -phosphoribosyl-5-amino-4-imida2olecarboxamide DAP = diaminopimelic acid PRPP = phosphoribosyl pyrophosphate a — KGA = a-ketoglutaric acid Orn = ornithine Cit = citnilline represents the one carbon unit lost to tetrahydrofolate as serine is converted to glycine. 

FIGURE 50-3 Intracellular activation of nucleoside analog reverse transcriptase inhibitors. Drugs and phosphory-lated anabolites are abbreviated the enzymes responsible for each conversion are spelled out. The active antiretroviral anabolite for each drug is shown in the blue box. Key ZDV, zidovudine d4T, stavudine ddC, dideoxycytidine FTC, emtricitabine 3TC, lamivudine ABC, abacavir ddl, didanosine DF, disoproxil fumarate MP, monophosphate DP, diphosphate TP, triphosphate AMP, adenosine monophosphate CMP, cytosine monophosphate dCMP, deoxycytosine monophosphate IMP, inosine 5 -monophosphate PRPP, phosphoribosyl pyrophosphate NDR, nucleoside diphosphate. 

The enzyme 5-phosphoribosyl-l-pyrophosphate (PRPP) synthetase (EC 2.7.6.l) catalyzes the synthesis of PRPP from ribose-5-phosphate (R-5-P) and adenosine 5 triphosphate (ATP) in the presence of magnesium and inorganic phosphate (9-ll). In the present communication we report studies on a mutant superactive PRPP synthetase in the erythrocytes of two brothers with excessive purine production associated with gout and uric acid lithiasis. In these two patients the serum uric acid reached 13.5 and 13.6 mg percent and the urinary 24 hours uric acid excretion 2400 mg and 2250 mg, respectively. All other members of the family examined were clinically and biochemically normal, except for the mother of the patients who had hyperuricosuria, 1100 mg per 24 hours. 

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