Purine Nucleotide Biosynthesis Is Regulated by Feedback Inhibition

Three major feedback mechanisms cooperate in regulating the overall rate of de novo purine nucleotide synthesis and the relative rates of formation of the two end products, adenylate and guanylate (Fig. 22-35). The first mechanism is exerted on the first reaction that is unique to purine synthesis—transfer of an amino group to PRPP to form 5-phosphoribosylamine. This reaction is catalyzed by the allosteric enzyme glutamine-PRPP amidotransferase, which is inhibited by the end products IMP, AMP, and GMP. AMP and GMP act synergisti-cally in this concerted inhibition. Thus, whenever either AMP or GMP accumulates to excess, the first step in its biosynthesis from PRPP is partially inhibited.

In the second control mechanism, exerted at a later stage, an excess of GMP in the cell inhibits formation of xanthylate from inosinate by IMP dehydrogenase, without affecting the formation of AMP (Fig. 22-35). Conversely, an accumulation of adenylate inhibits formation of adenylosuccinate by adenylosuccinate synthetase, without affecting the biosynthesis of GMP. In the third mechanism, GTP is required in the conversion of IMP to AMP (Fig. 22-34, step ®), whereas ATP is required for conversion of IMP to GMP (step (4), a reciprocal arrangement that tends to balance the synthesis of the two ribonucleotides.

The final control mechanism is the inhibition of PRPP synthesis by the allosteric regulation of ribose phosphate pyrophosphokinase. This enzyme is inhibited

Imp Xmp Gmp

FIGURE 22-34 Biosynthesis of AMP Xanthylate Guanylate and GMP from IMP. (XMP) (GMP)

FIGURE 22-34 Biosynthesis of AMP Xanthylate Guanylate and GMP from IMP. (XMP) (GMP)

ribose phosphate pyrophosphokinase (PRPP synthetase)

Ribose 5-phosphate

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  • Bilba
    How purine nucleotides is regulated?
    8 years ago

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