Polyglutamic acid biosynthesis

The intensive studies on the genetic code and on the proteins in recent years have led to a fairly good understanding of the mechanism of protein biosynthesis . The biosynthetic mechanism involved in the formation of peptides has not yet been studied in equal detail. Some physiologically active peptides like bradykinin and angiotensin are known to be derived from proteins by a specific enzymatic hydrolysis. Other peptides, like glutathione - , ophthalmic acid , the nucleotide-pentapeptide from Staph, aureus and y-polyglutamic acid have been shown to require for their synthesis only a soluble enzyme system. Their biosynthetic mechanism is therefore entirely different from that of the proteins. Such a different type of mechanism has also been demonstrated lately to be involved in the synthesis of peptide antibiotics. 

Folacin (folic acid) is involved in metabolism and in the biosynthesis of purines and pyrimidines. It is a very stable vitamin but does not occur naturally in feedstuffs. Instead it occurs in reduced forms as polyglutamates, which are readily oxidized. These forms are converted to folic acid in the body. Diets commonly contain sufficient folacin but this is not assured. Folacin is therefore usually included in the vitamin supplement added to poultry diets to ensure adequacy. A deficiency in young chicks or poults results in retarded growth, poor feathering and perosis. Coloured plumage may lack normal pigmentation, and a characteristic anaemia is also present. Cervical paralysis is an additional symptom in deficient turkeys. 

The details of the pathway for de novo biosynthesis are shown in Fig. 15-16. The amino acid L-glutamine is the substrate providing nitrogen atoms for reactions 1, 4 and 14, catalyzed by amido phosphoribosyltransferase, FGAM synthetase and GMP synthetase, respectively. Glycine is a substrate at reaction 2, and L-aspartate at reactions 7 and 11. P-Rib-PP is a substrate and activator for amidophosphoribosyltransferase, which is subject to inhibition by AMP. IMP and GMP and by polyglutamate derivatives of dihydrofolate. 

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