Ribosylamine phosphate synthesis

The possible physiological role of ammonia as a nitrogen donor for ribosylamine phosphate synthesis has been studied and debated. Although ammonia can react nonenzymatically with PP-ribose-P to form riboiqrl-amine phosphate (IS), it can also react enzymatically to form this product in cell extracts (H, 15) and in intact cells (16, 17). Although most work supports the role of PP-ribose-P amidotransferase as the enzyme involved, Reem (18) has put forward evidence that a separate enzyme might use ammonia exclusively. 

The answer is c, (Murray, pp 375-801. Scriver, pp 2513-2570. Sack, pp 121-138. Wilson, pp 287-320.) 5 -phosphoribosyl-l-pyrophosphate (PRPP) donates the ribose phosphate unit of nucleotides and is absolutely required for the beginning of the synthesis of purines. In fact, the enzymes regulating the synthesis of PRPP and the subsequent synthesis of phospho-ribosylamine from PRPP are all end product-inhibited by inosine... 

The substrate for this reaction, ct-D-ribose-5-phosphate, is a product of the pentose phosphate pathway.) Figure 14.24 illustrates the initial phase in the pathway by which PRPP is converted to inosine monophosphate (inosinate), the first purine nucleotide. The process begins with the displacement of the pyrophosphate group of PRPP by the amide nitrogen of glutamine in a reaction catalyzed by glutamine PRPP amidotransferase. This reaction is the committed step in purine synthesis. The product formed is 5-phospho-/3-D-ribosylamine. 

Depressed synthesis or the total absence of glycine causes the accumulation of 5-phospho-/J-D-ribosylamine, the other substrate of the enzyme phosphoribosylglycinamide synthase. Reaction of pyridoxyl phosphate with alanine ... 

From studies such as these it has been concluded that the major site of action of 6-MP and its transformation products is in preventing the conversion of IMP to either SAMP or XMP (Fig. 5). By feed-back inhibition the accumulated IMP prevents the formation of ribosylamine-5-phosphate. The main cytotoxic events following administration of 6-MP are then likely to result from inhibition of both RNA and DNA synthesis, at early stages in the de novo synthesis of purines. 

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