236 H. M. KALCKAR VOL. 4 (1950) 



two purines bases which according to the studies on the intact organism are not incor- 

 porated into the nucleic acids. We are forced to conclude therefore that the type of 

 incorporation of purines which can be demonstrated in incubates with liver enzymes does 

 not represent the final way by which the intact organism incorporates purines for the 

 maintenance of its protoplasmic nucleic acids. It is even justified to question whether 

 the nucleoside phosphorylase has anything whatever to do with the incorporation of 

 purines into nucleic acids. The nucleoside phosphorylase might for instance play a role 

 in processes other than the incorporation of purines into nucleic acids. This brings us to 

 recall the situation with respect to the amino acid oxidases around 1936. At that time 

 Krebs described a water soluble oxidase which catalysed the oxidation of the d-amino 

 acids and which Warburg and Christian purified and identified as a flavine enzyme. 

 Six to seven years later Green, Ratner, and Nocito isolated the oxidase which catal- 

 ysed the oxidation of 1-amino acids and this also proved to be flavoprotein. When we 

 talk about protein metabolism especially combustion of proteins in the animal organism 

 we realize that the oxidation of the amino acids from proteins must be catalysed by 

 the 1-amino acid oxidase and not by the d-amino acid oxidase. The physiological function 

 of the latter enzyme still remains obscure. We may apply the same point of view to- 

 wards the nucleoside phosphorylase. It appears unlikely that the enzyme should simply 

 serve in the breakdown of purine compounds since, as mentioned earlier, in an enzymatic 

 mixture of free purine, phosphate, nucleoside and phospho-riboside the equilibrium is 

 definitely favourable towards nucleoside formation. The possibility should not be over- 

 looked that formation of inosine from ribose-1-phosphate catalysed by liver nucleoside 

 phosphorylase might represent a primary step in the synthesis of purine ribosides 

 prior to the incorporation of adenine. Adenine might then be exchanged directly with 

 the hypoxanthine present in inosine by an enzyme which does not occur in our usual 

 enzyme preparations. The catalytical action of inosine on the deamination of adenine 

 by a bacterial enzyme^^ might be explained on this assumption; in vitro studies with 

 labelled carbon or nitrogen in the adenine ring should be able to clarify this problem. 

 As regard to the incorporation of pyrimidine into nucleic acid little is known. The recent 

 team work between Bergstrom and Hammarsten and his group^^ has shed interesting 

 light on this problem. It was found that N^^ labelled orotic acid can be used as a pre- 

 cursor of the ribonucleic acid pyrimidines of the adult rat. The question regarding in- 

 corporation of purines and pyrimidines into desoxyribonucleic acids brings up important 

 new problems regarding the rejuvenation of nuclear components. It is known from the 

 studies by Brues, Tracy, and Cohn and as well as by Hammarsten and Hevesy 

 that the phosphorus in the desoxyribonucleic acids is renewed at a much slower rate 

 than that incorporated in ribonucleic acids. In regenerating or growing tissues the 

 renewal of desoxynucleic acid phosphorus is increased markedly. Likewise Brown and 

 coworkers^' found that the rate of incorporation of N^-^ adenine into desoxyribonucleic 

 acid in the adult rat is negligible as compared with the corresponding processes taking 

 place in the ribonucleic acid. These observations indicating a very slow turnover of 

 desoxyribonucleic acid components in the adult organism coupled with the knowledge 

 of the existence of a highly active desoxynucleoside phosphorylase poses several new 

 questions. For example the enzymatic system catalysing degradation and synthesis of 

 desoxynucleosides in liver should be taken into account in considering the regulatory 

 mechanisms which control transitions between resting and growing states. 



As concluding remarks I should like to add that the two types of approaches, the 

 References p. 237 . 



