Amidophosphoribosyl transferase

Answer D. IMP is a feedback inhibitor of PRPP amidophosphoribosyl transferase, the first reaction in the biosynthesis of purines. IMP is formed by the HPRT reaction in the salvage of hypoxanthine. 

The regulation of purine nucleotide biosynthesis occurs at four points in the pathway. The enzymes PRPP synthetase, amidophosphoribosyl transferase, IMP... 

Regulation of purine synthesis occurs at several sites (Fig. 41.9). Four key enzymes are regulated PRPP synthetase, amidophosphoribosyl transferase. 

The rate-limiting enzyme in the synthesis of purine nucleotides is amidophosphoribosyl transferase (also known as phosphoribosylpyrophosphate amido transferase), which is a major target for one of the two thiol-containing purine anticancer antimetabolites on the U.S. market. 

Glucose 6-phosphatase is present in the liver and kidneys but not in muscle. Amidophosphoribosyl transferase, the enzyme that catalyzes the committed step in the biosynthesis of purine nucleotides, is inhibited by all purine nucleotides. 

The feedback inhibition of the first specific enzyme of purine biosynthesis, amidophos-phoribosyltransferase, by the purine ribonucleotides AMP and GMP was described in a partially purified enzyme system over 20 years ago(l). The molecular basis for this inhibition, namely the aggregation of active subunits to an enzymatically inactive larger form in the presence of purine ribonucleotides, was described with the amidophosphoribosyl-transferase obtained from human placenta seven years ago(2). Phosphoribosylpyrophos-phate (PRPP) activates the mammalian enzyme by causing disaggregation of the inhibited large form to the catalytically active small form. 

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