114 NITROGEN METABOLISM 



exopeptidases, cannot hydrolyse bonds involving D-amino- 

 acids. Bergmann and Fruton's investigations appeared to show 

 that the specificity of the endopeptidases with regard to the 

 amino-acid composition of the bonds they attacked was rela- 

 tively high, and this was particularly so in the case of pepsin. 

 But as more peptides have been synthesized and tested [see 

 2], it has become clear that these enzymes are not so specific 

 as the results of the earlier work might suggest. Though few 

 of them have yet been purified, it is evident that there are 

 a number of dipeptidases, amino- and carboxy-polypepti- 

 dases and it is possible that each one has different specificity 

 requirements. 



In addition to the extracellular enzymes, there are a num- 

 ber of intracellular animal proteases known as kathepsins, of 

 which four types are known, analogous to pepsin, trypsin, 

 amino-polypeptidases and carboxy-polypeptidases respec- 

 tively as regards their specificity. Unlike the extracellular 

 enzymes, the kathepsins are only active in the presence of 

 an activator such as HgS, cyanide, cysteine or glutathione, 

 and in this respect they are very similar to some of the 

 intracellular proteases of micro-organisms. 



Great interest has been taken in the mammalian extra- 

 cellular proteases known to be secreted in the form of an 

 inactive precursor, a zymogen, the crystalline form of which 

 is different from the corresponding active enzyme. Pepsino- 

 gen is converted to pepsin by treatment with acid or with 

 pepsin itself, whilst trypsinogen is activated by enterokinase 

 or by trypsin. Activation of the precursor may involve the 

 removal of a small peptide (as with pepsinogen) or the open- 

 ing of a small number of peptide bonds (chymotrypsinogen 

 and trypsinogen). 



There is at present conflicting evidence as to the manner 

 in which proteins and peptides are hydrolysed by the endo- 

 peptidases to smaller units. The enzyme may attack all the 

 susceptible peptide links in any one peptide chain simul- 

 taneously and thus release the component amino-acids and 

 peptides concurrently (the 'all or none' hypothesis). Alterna- 

 tively, it may attack the peptides in a random manner, hydro- 

 lysing only one bond at a time in any one peptide, until the 



