PEPTIDES AND PROTEINS 99 



acid participates have yet to be isolated, there are good 

 reasons for beUeving that it is impUcated in the synthesis 

 ofcertainamino-acids, purines and pyrimidines (pp. 146-51). 

 Glutathione (GSH), the first peptide to be assigned the 

 function of a co-factor in intermediary metabolism, was dis- 

 covered and isolated by Hopkins from yeast and various 

 animal tissues. Little is known about the distribution of this 

 peptide in bacteria [4] and its isolation from these organisms 

 has not yet been reported. The chemical synthesis of GSH 

 by Harington and Mead provided conclusive proof that it 

 was y-glutamylcysteinylglycine. Ever since GSH was known 

 to contain a thiol group, it has been postulated that GSH 

 entered into cellular oxido-reduction reactions: 



2GSH —^ OS— SG + 2H 



In the presence of glutathione reductase, an enzyme found 

 in yeast, plants and animals, oxidized glutathione will accept 

 hydrogen from reduced TPN but not DPN: the reverse re- 

 action has not yet been demonstrated [6]. The activity of 

 many enzymes is inhibited by substances which react with 

 or oxidize thiol groups, and it is therefore possible that GSH 

 is part of the mechanism whereby these enzymes are main- 

 tained in or brought into an active state in vivo. Glutathione 

 takes an active part [34] in the conversion of methylglyoxal 

 to lactic acid, a reaction catalysed by the enzyme system 

 glyoxalase, found for example in Esch. colt and Sac. cere- 

 visiae. Racker and Krimsky [35] have shown that GSH is 

 tightly bound to the enzyme triosephosphate dehydrogenase, 

 and they suggest that a thiol ester of 3-phosphoglyceric acid 

 is an essential intermediate stage in the formation of 1:3- 

 diphosphoglyceric acid (cf. the role of Co. A in the pyruvic 

 oxidase system). Certain reactions in which GSH partici- 

 pates as a substrate rather than as a co-factor have recently 

 aroused great interest because of their potential significance 

 in the synthesis of peptides and proteins in vivo. Working 

 with cell-free preparations of sheep kidney, Hanes, Hird and 

 Isherwood [16] have demonstrated that the y-glutamyl 

 group of GSH and other y-glutamyl peptides (but not 

 glutamine) can be transferred to peptides or to amino-acids, 



