170 S. S. COHEN 



CH.SH NH2 CH3 CH3 



r I \/ 



CHNH — COCH2CH2CH CH 



I I + I 



CO-NHCH2COOH COOH HOOCCHNH2 



J 



r 



CHjSH CH, CH, 



I \/ 



CHNH2 C NH2 



I "*" I I 



CONHCH2COOH HOOCCHNH-COCH2CH2CH 



COOH 

 glutathione + valine ^ cysteinylglycine + glutamylvaline 



(XXIV) 



It lias been suggested that a y -glutamyl group may be a removable 

 .pbysiological acyl substituent at the amino group of an ammo acid in the 

 course of biosynthesis of a peptide involving the carboxyl of the amino acid. 



The extension of peptide chains may be effected at the expense of amides 

 in the presence of a proteolytic enzyme, as foUows: 



chymotrypsin 



benzoyl tyrosineamide + glycineamide > benzoyltyrosyl- 



glycineamide -f NH3 (1) 



ficin 



carbobenzoxy isoglutamine +11 metliionineamide > IONH3 + 



carbobenzoxy glutamyl (methionyl)io methionineamide (2) 



The initial intermediate in the latter reaction is probably carbobenzoxy 

 glutamyl methionineamide. Such reactions have produced an increased 

 appreciation of the possibihty of a relatively high free energy of hydrolysis of 

 some amide bonds. The existence of terminal amide bonds in hormones like 

 vasopressin and oxytocin suggests the possibihty of a role of these bonds in an 

 initial formation of a peptide bond in the physiological functioning of these 

 hormones. It should be noted that the heat of hydrolysis (free energy data are 

 unavailable at present) of the — CONH2 bond is of the same order of magni- 

 tude as that of inorganic pyrophosphate. The enzymatic exchange of the 

 NH3 in the amide of glutamine with hydroxylamine (NHgOH) does require 

 an initial activation by ATP. Thus, although it is conceivable that proteo- 

 lytic enz}Tnes or transpeptidases may play some role in the extension of 

 polypeptide chains, nevertheless the initial formation of glutamyl bonds or 

 amides as in exchangeable glutamine or isoglutamine may be expected to 

 require an activation of the carboxyl group following some other energy- 

 yielding reaction, such as the hydrolysis of a pyrophosphate group in ATP. 



