116 Essays in Biochemistry 



This product was obtained in a yield of 86% of the theory, based on 

 the amount of NH 4 + liberated. Clearly, what had occurred was the 

 proteinase-catalyzed polymerization of the dipeptide amide by two 

 successive transamidation reactions. It is extremely probable that at 

 each step, an alanylphenylalanyl unit was added to the amino end 

 of the growing peptide chain, in a manner analogous to the action 

 of crystalline muscle phosphorylase, which catalyzes the successive 

 addition of glucosyl units of glucose-1 -phosphate to the non-reducing 

 end of a growing amylose chain. 



There can be no doubt, therefore, that the known intracellular 

 proteinases can catalyze transamidation reactions in which peptide 

 chains are lengthened and that these enzymes exhibit considerable 

 specificity in these reactions. However, no information is available 

 about the role of the cathepsins in the metabolism of intact animal 

 cells, and nothing can be said at present about the actual occurrence 

 of transamidation reactions in the biosynthesis of proteins. All that 

 can be stated is that the intracellular proteinases are the only well- 

 defined cellular catalysts known to exhibit the specificity to be expected 

 of enzymes that could participate in protein synthesis. One may 

 therefore propose, as a working hypothesis, that a multienzyme system, 

 composed of a number of intracellular proteinases, is responsible for the 

 specific elongation of the peptide chains of proteins. According to this 

 view, the characteristic sequence of amino acid residues in peptide 

 chains is the consequence of the coupled action of a series of proteinases 

 that differ in specificity. An objection that has been raised against 

 this proposal is the difficulty of imagining a sufficiently large number 

 of proteinases that may be expected to be needed to make one type 

 of protein and the much larger number required for the synthesis of 

 all the different proteins. However, there appears to be no valid 

 reason (other than the search for simplicity I against the participation 

 of a series of proteinases in the synthesis of a protein. Also, there 

 does not appear to be any a priori objection to the possibility that 

 a given proteinase could participate in the synthesis of more than one 

 protein. Certainly it would be more in accord with the knowledge 

 gained from the study of other biochemical processes, involving the 

 metabolic synthesis or degradation of molecules much simpler than 

 the proteins, to assume that a multienzyme system is involved. Such 

 an assumption is not incompatible with the experimental results that 

 have led to the formulation of the "template" hypothesis. If the term 

 "template" is considered to represent an organized cellular assembly 

 of enzymic catalysts (plus other constituents such as nucleic acids I 



