Principles of Biochemistry Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Biosynthesis of Amino Acids and Nucleotides
The biosynthesis of purine nucleotides is regulated by feedback inhibition

The Regulation of the overall rate of de novo purine nucleotide synthesis and the relative rates of Formation of the two end products, adenylic acid and guanylic acid, is mediated by three major feedback regulatory mechanisms (Fig. 22-18). The first of these mechanisms controls an early stage unique to this biosynthetic pathway, namely The transfer of an amino group to 5-phosphoribosyl-1-pyrophosphate (PRPP) to yield 5-phosphoribosylamine (Fig. 22-15). This reaction is catalyzed by an allosteric enzyme that is inhibited by the End products of the sequence, AMP and GMP. Consequently, whenever AMP and GMP accumulate in excess, the initial step of their Biosynthesis from PRPP is suppressed.

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Fig. 22-18. Feedback regulatory mechanisms governing the biosynthesis of adenylic and guanylic NUCLEOTIDES in E. coli. In other organisms, these biosynthetic pathways are regulated differently.

The second regulatory mechanism operates at a later stage (Fig. 22-18); here, an excess of cellular GMP allosterically inhibits The formation of GMP from inosinic acid while leaving AMP synthesis unaffected (Fig. 22-18). Conversely, under the third regulatory mechanism, the accumulation of adenylic acid suppresses its own formation without affecting GMP synthesis.