Phosphoribosyl ATP

This enzyme [EC 1.1.1.23] catalyzes the reaction of l-histidinol with two NAD+ to produce L-histidine and two NADH. L-Histidinal will also serve as a substrate for this protein. The Neurospora crassa enzyme will also catalyze the reactions of phosphoribosyl-AMP cyclohydrolase [EC 3.5.4.19] and phosphoribosyl-ATP pyrophosphatase [EC 3.6.1.31]. 

This enzyme [EC 3.5.4.19] catalyzes the hydrolysis of 5-phosphoribosyl-AMP to produce 5-(5-phospho-D-ribo-sylaminoformimino)-l-(5-phosphoribosyl)tmidazole-4-carboxamide. The enzyme isolated from Neurospora crassa can also catalyze the reactions of histidinol dehydrogenase and phosphoribosyl-ATP pyrophosphatase. 

PRPP is the activated intermediate in the synthesis of phosphoribosylamine in the de novo pathway of purine formation of purine nucleotides from free bases by the salvage pathway of orotidylate in the formation of pyrimidines of nicotinate ribonucleotide of phosphoribosyl ATP in the pathway leading to histidine and of phosphoribosylanthranilate in the pathway leading to tryptophan. 

CpG0141 Histidinol dehydrogenase C0Gbl40 Phosphoribosyl-ATP pyrophosphol-... 

Figure 5.82 Biosynthesis of histidine. PRPP, 5-phosphoribosyl-a-l-pyrophosphate PRATP, AT-5 -phosphoribosyl-ATP PRAMP, M-S -phosphoribosyl-AMP 5 -ProFAR, yV -[(5. phosphoribosyl)-formimino]-5-aminoiinidazole-4-carboxamide-ribonucleotide 5 -PRFAR, A/ -[(5 -phosphoribulosyl)-formimino]-5-aminoimidazole-4-carboxainide-ribonuc leotide IMGP, imidazole glycerol-phosphate AICAR, 5 -phosphoribosyl-4-carboxamide-5-aminoimidazole lAP, imidazoleacetol-phosphate HOL-P, L-histidinol-phosphate HOL, L-histidinol HAL, L-histidinal.

Fig. 1. Interconversions of purine nucleotides. The wavy line indicates activation the broken lines indicate inhibition. PR-ATP, N-l- phosphoribosyl-ATP S-AMP, adenylo-succinic acid AICAR, phosphoribosyl-aminoimidazolecarboxamide.

Direct deamination of AMP to IMP by adenylate aminohydrolase (EC 3.5.4.6) occurs primarily in mammalian systems. It plays little, if any, role in bacteria where conversion usually occurs indirectly via deamination of adenine or adenosine [113,114]. Little is known about regulation at these levels, although adenosine deaminase is inducible by its substrate [114] and mutants lacking it have been obtained [115], Another indirect conversion in bacteria involves the regeneration of AlCAR, in the eventual conversion of phosphoribosyl-ATP (PR-ATP) to histidine. The AlCAR so obtained reenters the biosynthetic pathway and IMP is produced [33]. This pathway is regulated by histidine which exerts a profound feedback inhibition at the level of PR-ATP formation from ATP [116]. 

Abbreviations used PRPP, phosphoribosylpyiophosphate PR-ATP, phosphoribosyl-ATP PR-AMP, phosphoribosyl-AMP PR-AIC, 4-amino-S-iinidizolecarboxainide ribonucleotide ribosyl-AIC, 4-amino-S-imidazoIecarboxamide ribonucleoside TRA, 1,2,4-triazole-3-alanine. 

ATP phosphoribosyltransferase 2 phosphoribosyl-ATP pyrophosphatase 3 phosphoribosyl-AMP cyclohydrolase 4 isomerase 5 formyltransferase, inosine monophosphate cyclohydrolase 6 adenylosuccinate synthetase 7 adenylosuccinate lyase 8 adenylate kinase 9 imidazole glycerol phosphate dehydratase 10 histidinol phosphate aminotransferase 11 histidinol phosphatase 12 histidinol dehydrogenase... 

The role of purines in the biosynthesis of the imidazole ring of histidine has been investigated in baeteria. The use of labeled purine bases (guanine and adenine) followed by the chemical breakdown of newly formed histidine established that the and the C2 of the purine base were incorporated in the N3 and C2 of the imidazole ring of histidine. The N3 of the imidazole ring was shown to be derived from glutamine. On the basis of further studies on cell-free preparations, the biosynthetic pathway of the imidazole ring of histidine ean now be outlined. Ribose-1-phosphate reacts with ATP to yield phosphoribosyl pyrophospate and AMP PRPP reacts with ATP to form a new complex assumed to be phosphoribosyl ATP. Phosphoribosyl (PR) ATP is then converted to PR AMP by a specific... 

The final amino acid to be considered here is histidine (His, H). As shown in Scheme 12.26, the initial steps begin with the reaction of ribose-1,5-diphosphate with ATP in the presence of ATP-phosphoribosyl transferase (EC 2.4.2.17) then, after phosphate is lost (phosphoribosyl-ATP diphosphatase [EC 3.6.1.31]), the pyrimidine ring is hydrolytically cleaved (phosphoribosyl-adenosine 5 -phosphate [AMP] cyclohydrolase [EC 3.5.4.19]), a process that is followed by the opening of... 

Fig. 4. Histidine tnosynthess. Intermediates PRPP, phosphoribosyl pyrophosidiate PR-ATP, JV-phoqjhoribosyl-ATP PR-AMP, A/ -phosphoribosyl-AMP PR-FAIC-RN, phosphoribosyl for-mimino-S-amino imidazole carboxamide ribonucleotide PRu-FAIC-RN, phosphoribulosyl for-mimino-5-aniino imidazole carboxamide ribonucleotide IGP, imidazole glycerol phosphate lAP, imidazole acetol idrosphate HP, histidinol (dioqrhate HOL, histidinol. Enzymes (I) ATP phos-phoribosyltransferase (EC 2.4.2.17) (2) phosphoribosyl-ATP pyrophosphohydrolase (EC 3.6.1.31) (3) idiospharibosyl-AMP cyciohydrolase (EC 3.5. A19) (4) PR-FAIC-RN isomerase (EC S.3.1.16) (S) glutamine amidotransferase (6) cyclase (7) imidazole glycerol phosphate dehydratase (EC 4.2.1.19) (8) histidinol-phosphate aminotransferase (EC 2.6.1.9) (9) histidinol phosphatase (EC 3.1.3.15) (10) histidinol dehydrogenase (EC 1.1.1.23).

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