Purine nucleotides synthesis, PRPP precursor

However, since the fate of the PRPP can be to form purine nucleotides, pyrimidine nucleotides, or coenzymes, the control must be complex and not limited to only purine nucleotides, pyrimidine nucleotides, or coenzymes. The next enzyme under control by purine nucleotides is PRPP transamidinase, catalyzing the formation of the phosphoribosyl amide (PRPP + glutamine PRNH2 + glutamate + pyrophosphate), the first unique precursor of purines. Since the synthesis ofPRPP is slow, there must be controls to allow its utilization in other processes when purine nucleotide pools are satisfied. The control of this system is interesting and shows the phenomena of synergism. That is, AMP, the product of one branch of the pathway, can inhibit the enzyme activity approximately 10% GMP, the product of the other branch of the pathway, can also cause approximately a 10% inhibition. 

The purine ring is assembled from a variety of precursors glutamine, glycine, aspartate, N formyltetrahydrofolate, and (XT. The committed step in the de novo synthesis of purine nucleotides is the formation of 5-phosphoribosyIamine from PRPP and glutamine. The purine ring is assembled on ribose phosphate, in contrast with the de novo synthesis of pyrimidine nucleotides. The addition of glycine,... 

The mdstence of a feedback control mechanism for purine biosynthesis was suggested by the observation that unlabeled purines inhibited purine theris de novo from labeled precursors in several systems (SB, 1B4,445-447). Initially, it was postulated that the feedback inhibition by preformed purines may have involved a shuntii of PRPP from the de novo route of purine biosyntheris and utilization of PRPP for nucleotide formation from the purine base and PRPP. PRPP was an obligatory intermediate in the synthesis of purines de novo. Since the nucleotide was still formed albeit by a different route, this would not be considered a feedback mechanism. It is probable, however, that the accumulation of the newly-formed nucleotide from PRPP and base inhibited the de novo route. 

Non- oxidative branch Pentose-5 -Phosphates Ribose-5-P 2 deoxy ribose-5-P 5 -phosphoribosyl-1 -pyrophosphate (PRPP) i) Structural components of nucleotides a. Basal structural component of RNA b. Basal structural component of DNA c. Precursor of both de novo and salvage synthesis of nucleotides ii) Intermediate products of purine metabolism and act as precursor molecules of cofactors, e g., riboflavin, flavin mononucleotide (FMN), flavin adenine di nucleotide (FAD) iii) Precursor of the amino acid. Histidine. 

In proliferating cells purine nucleotides - necessary for DNA- and RNA-synthesis - can be formed by incorporation of small precursors (de novo pathway) and by utilisation of free purin bases (salvage pathway). The most important reactions of both metabolic pathways are demonstrated in figure 1. The first reaction of the de-novo pathway - the formation of phosphoribosylamine from glutamine and phosphoribosyIpyrophosphate (PRPP) by the enzyme PRPPamidotransferase - is the target of a negative feed back control mechanism by the endproducts IMP/GMP and AMP (1). 

The answer is a. (Murray, pp 812—828. Scriver, pp 2537-2570. Sack, pp 97—158. Wilson, pp 287-320.) The child has Lesch-Nyhan syndrome (308000), an X-linked recessive disorder that is caused by HGPRT enzyme deficiency. HGPRT is responsible for the salvage ol purines from nucleotide degradation, and its deficiency elevates levels ol PRPP, purine synthesis, and uric acid. PRPP is also elevated in glycogen storage diseases due to increased amounts of carbohydrate precursors. 

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