THE BIOLOGICAL CONVERSION OF I-SI(:RIN# TO Gl,Y(:In’E

The amino acid glycine is involved not only in protein formation but in t,he synthesis of glutathione, creatine (l), and the protoporphyrin of hemoglobin (2). However, the mechanism by which the animal organism forms glycine is cluite obscure. It has been generally considered that the “nonessential” amino acids are synthesized from a-keto acids either by amination with ammonia or by transamination. However, some of the amino acids can be synthesized in the animal cell by transformation of one into another! with utilization of the carbon structure as well as the nitrogen. Evidence has been obtained for the interrelationship of glutamic acid, proline (3, 4), and ornithine (5, G), of phenylalanine and tyrosinc (7), and the conversion of serine into cystine (8, 9). The observation of Keubauer (10) that phcnylglycine gives rise to phenylglyoxylic acids led to the hypothesis that glycinc may be formed by a reverse process; i.e., by amination of glyoxylic acid. Interest in this hypothesis has rccent’ly been revived by the finding of Ratner, Nocito, and Green (11) that an enzyme exists in liver and kidney which catalyzes the oxidation of glycine to glyoxylic acid and ammonia. However, Haas (12) and Sassa (13) were unable to demonstrate any formation of glycine from this acid in perfusion and feeding cxperimcnts. It has been po&lated by Knoop (14, 15) that a-amino-Shydroxy acids undergo fl oxidation to yield glycine, since it had been found that ,+phenylserine (14, 16) and &phenyl-a-amino-p-hydroxyvaleric acid (15) both yielded hippuric acid when administered to a dog. However, the theory actually sheds no light on the nature of the first 2-carbon fragment that is split off, for benzoic acid should be formed from these odd numbered acids, which in turn would give rise to hippuric acid, regardless of the nature of the 2-carbon fragment. Recently, Leuthardt (17,18) found that on incubat,ion of guinea pig liver slices with benzoic acid and glutamine, or dl-serine, or asparagine, or Z-glutamic acid, or proline there was an increase in the a-amino nitrogen in the hydrolyzed ether extract, presumably arising from the hydrolysis of hippuric acid. The most decided increases were produced by glutamine and serine. This finding was.positive only in the guinea pig. Leuthardt suggested that both glutamine and serine were converted to glycine in the