PEPTIDES AND PROTEINS IO5 



and number of bonds in the products is the same as in the 

 reactants, they proceed with Httle overall change in free 

 energy and are therefore independent of the availability of 

 metabolic energy. Several typical proteol}1;ic enzymes are 

 known to catalyse transpeptidation reactions, and further- 

 more, to lengthen a peptide chain by the direct coupling of 

 peptides. Thus, with chymotrypsin [ii]: 



benzoyl-L-tyrosinamide+glycinamide ^ 



benzoyl-L-tyrosylglycinamide+NHs 

 benzoyl-L-tyrosine+glycinamide ?^ 



benzoy 1-L-ty rosylgly cinamide + H 2O 



It is therefore possible, as suggested many years ago, that 

 the action of the proteases is reversible and that in the 

 appropriate conditions they catalyse the synthesis and not 

 the hydrol^'sis of peptides and proteins. Transpeptidation 

 reactions involving GSH have already been described (p. 99). 

 Because cysteinylglycine is readily hydrolysed by cellu- 

 lar enzymes and yet is relatively stable when combined, as 

 in glutathione, Hanes and his colleagues proposed that the 

 attachment of a y-glutamyl radical to a peptide confers re- 

 sistance to hydrolysis by intracellular proteases, and in con- 

 sequence, synthesis is favoured and the peptide chain can 

 be gradually lengthened by successive transfer reactions. 

 Several bacteria catalyse exchange reactions between the 

 amide group of asparagine or glutamine and hydroxylamine 

 or isotopically labelled NHt: with NHgOH, such reactions 

 lead to the formation of aspartyl- and glutamyl-hydroxamic 

 acid respectively [45]. Whether the amide group can likewise 

 be replaced by an amino-acid or peptide is not known. Pro- 

 tein synthesis may therefore be visualized as a stepwise 

 process beginning with glutathione, and possibly glutamine, 

 as a source of peptide bonds synthesized at the expense of 

 energy derived from ATP, and by means of transpeptidation 

 reactions the amino-acid components of such bonds are 

 subsequently altered so as to form peptides from which 

 specific proteins are synthesized by further transfer and 

 coupling reactions [11]. 



