112 Essays in Biochemistry 



amino acids are administered to an animal, and if discrete proteins 

 are isolated from the tissues or body fluids, every residue of a given 

 labeled amino acid in the peptide chain has the same isotope content. 

 In a striking experiment, Simpson and Velick 8 administered to a rabbit 

 five isotopic amino acids, and 38 hours later isolated from the muscle 

 highly purified samples of two enzymes (aldolase and glyceraldehyde- 

 3-phosphate dehydrogenase). Upon analysis of 11 of the amino acids 

 obtained after hydrolysis, these investigators found that the ratio of 

 specific radioactivity of each of these amino acids in aldolase to the 

 specific activity of the same amino acid in the dehydrogenase was 

 constant. Subsequent work by Simpson, in which the animal was sacri- 

 ficed 30 minutes after the administration of the labeled amino acids, 

 gave essentially the same result. The logical conclusion drawn from 

 these experiments, and from similar studies performed by others (Neu- 

 berger et al, Work et al.), is that the systems involved in the syn- 

 thesis of the proteins under investigation were drawing on a single 

 "pool" of each of the amino acids. Although these experimental find- 

 ings are in accord with the "template" hypothesis, it has been pointed 

 out that they may also be interpreted in terms of either the rapid 

 successive formation of peptide bonds without the release from the 

 protein-synthesizing system of intermediates that accumulate, or the 

 existence of very small "pools" of intermediate peptides that equilibrate 

 rapidly with the amino acid "pools." 



Experiments on the induced formation of bacterial enzymes, espe- 

 cially those reported by Monod and by Spiegelman, have also been 

 interpreted to indicate that the synthesis of adaptive enzymes proceeds 

 by a "template" mechanism, without the intervention of peptide inter- 

 mediates. For example, it has been reported" that, in the induced 

 formation of /}-galactosidase during the growth of Escherichia coli, the 

 enzyme protein is derived from free amino acids in the medium rather 

 than from products of the cleavage of pre-existent bacterial proteins. 

 Here again, the results are consistent with the "template" mechanism, 

 but it is difficult to accept them as proof for its existence, so long as 

 alternative interpretations are not excluded. Other studies in bacterial 

 systems, notably those of Gale, 10 have focused attention anew on the 

 role of nucleic acids in protein synthesis and their possible function in 

 serving as "templates." That there is an intimate metabolic relation 

 between cellular nucleic acids and cellular proteins cannot be denied, 

 but it seems premature to interpret the available knowledge as favor- 

 ing the role of nucleic acids as "templates" in protein synthesis, espe- 

 cially since the "template" hypothesis itself is so insecurely founded. 



