The Metabolism of Proteins and Amino Acids

Abstract

I Protein synthesis.-The mechanisms of intracellular protein synthesis continue to remain obscure. The best demonstration to date of enzymatic peptide-bond synthesis is that reported by Bergmann and co-workers and reviewed by Bergmann & Fruton ( 1). Whether this mechanism, that is, peptide-bond synthesis by proteolytic enzymes, actually represents the chief intracellular pathway for protein synthesis is uncertain. The position of thermodynamic equilibrium of this type of reaction is almost completely in favor of hydrolysis and speaks against this mechanism unless one invokes special conditions which would allow the reaction to proceed toward synthesis; that is, re­ moval of synthetic products from the reaction medium due to insolu­ bility, change in ionic or molecular activity, more nearly anhydrous conditions, .etc. On the other hand, the proteolytic enzymes would seem to provide the factor of specificity which may be required for the synthesis of specific proteins. While reasoning by analogy is admit­ tedly dangerous, it is nevertheless of more than passing interest to note that with our increasing knowledge of intermediary metabolism such synthetic reactions as those of urea, glycogen and starch, sucrose, etc., have been shown to be catalyzed by enzyme systems totally unrelated to the simpler and better known corresponding hydrolytic enzymes. Since these syntheses are known to be coupled ultimately with oxida­ tion-reduction systems, the energy from which is transferred through intermediary phosphorylation reactions, it seems more than likely that peptide-bond synthesis is also coupled through energy rich phosphory­ lated intermediates with exergonic oxidation-reduction systems. It would appear that possible enzymatic systems coupling peptide-bond synthesis with high bond energy compounds of the phosphorylated type need to be investigated. The possibility exists that amino acids are phosphorylated on either the carboxyl or amino groups before conden­ sation occurs. It is further possible that amino acids are not coupled as such but rather as combinations of phosphorylated a-ketoacids and amino acids which give rise to ketopeptides [see Linderstr¢m-Lang