Glutamic acid glutathione synthesis

This is followed by removal of the glutamic acid and the glycine residues, which is followed by acetylation of the remaining cysteine. Essential amino acids are required for the synthesis of the proteins involved, pantothenic acid for coenzyme A synthesis, and phosphorus for synthesis of the ATP needed for glutathione synthesis. Similar scenarios can be developed for glucuronide and sulfate formation, acetylation, and other phase II reaction systems. 

We investigated the biosynthesis of component amino acids of glutathione (GSH) in vitamin-Bi2 or folic-acid deficient rats (1). Glycine-2-C or L-cystine-S was administered intraperitoneally to normal or the deficient rats. Liver GSH was determined, then isolated, and the radioactivity of GSH and its component amino acids was determined. The extent of incorporation of either glycine-2-C or cysteine-S into the respective moieties of GSH was not appreciably affected by either deficiency, indicating that neither vitamin is involved in the sjrstems which catalyze the synthesis of GSH from glycine, cysteine, and glutamic acid, a conclusion which is in accord with those of Bloch (2) and Snoke and Rothman... 

ATP is involved in the synthesis of hippuric acid and its analogs. The role of ATP is to form the aromatic acyl-Co A which then condenses with glycine to form the quasi-peptide. In the synthesis of glutamine from glutamic acid and ammonia Co A is not required, but ATP is. And in the synthesis of glutathione, the one case so far elucidated of an enzymatic... 

The enzyme for reaction (a) was shown not to be the same as that for the synthesis of glutamine from glutamic acid and ammonia. Neither did the purified enzymes for reactions (a) and (b) contain the enzyme that hydrolyzes glutathione. Therefore both transpeptidation and a transfer reaction analogous to 7-glutamyl transamidation are excluded from the mechanism of the synthesis of glutathione from its amino acids. 

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