Transpeptidation glutathione

It is unclear if the transpeptidation activity represents a way for glutathione to serve as a synthetic y-glutamyl donor or is simply an insignificant transferase activity typical of many hydrolases. This enzyme probably also participates in mercapturic acid formation, and this can be viewed as a variation of the direct hydrolysis reaction in which a substituted glutathione is substrate. 

The degradation of glutathione in animals and microorganisms probably takes place mainly by transpeptidation ... 

Recent reviews are available covering the general field of transpeptidation and transamidation reactions (1, 2, 3, 4) and these make unnecessary any detailed repetition here. It would seem appropriate at this Symposium, however, to consider whether the recognition of widespread transpeptidation reactions provides support for the view that glutathione (GSH) may act as an intermediary in the synthesis of protein. Our own view, as will become clear, is that this remains an attractive but still speculative hypothesis. 

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. 

Transpeptidation, obviously, does not explain the synthesis of new peptide bonds. It is to be expected that glutathione and glutamine will not remain the only examples of the synthesis of new peptide bonds. Transpeptidation by proteinases, each with its own specific requirements, however, may operate to provide redistribution of peptide bonds so that the manifold specificities of proteins are effected. ... 

Glutathione is known to participate, through its y-peptide linkage, in a transpeptidation reaction which may have an extraordinary interest as a mechanism for the synthesis of larger and more varied peptides and which has only begun to be investigated. The importance of glutathione in these transpeptidation reactions is difficult to evaluate until both the diversity and quantitative extent of such reactions are known. 

---