The biological asymmetry of glycerol.

In 1948, Ogston (1) postulated the existence of an asymmetric enzyme able to distinguish between one of two identical groups in a symmetrical compound. Shortly thereafter, Potter and Heidelberger (2) accomplished the biosynthesis of an “asymmetrically” labeled citric acid, substantiating Ogston’s principle. That glycerol, another compound of chemical symmetry, might also be biologically asymmetrical is suggested by the fact that only the L isomer of a-glycerophosphate, an intermediate in glycerol metabolism, is found in nature (3,4) or can be utilized by enzyme preparations (4, 5). If enzymes exerted no configurational specificity toward glycerol, thus permitting the formation of both Dand L-cY-glycerophosphate, then the D form must be either converted to the L isomer by a racemase or hydrolyzed by a specific phosphatase. In the absence of such enzymes, the incorporation into animal lecithins of some u-a-glycerophosphate synthesized from free glycerol arising from dietary triglycerides seems inevitable. Chemically synthetic glycerol labeled with Cl4 in the end carbon (6, 7) may be regarded as either glycerol-l-C4 or as glycerol-3-C4; hence it is not surprising that, when such glycerol is metabolized by rats, the isotope is found to be principally distributed among carbon positions 1, 3, 4, and 6 of glucose (8) or between carbons 1 and 3 of lactic acid (9). In the present study, glycerol-l-Cl4 was biosynthesized by yeast from glucose-3 ,4-C14, administered to rats, and the resulting glucose degraded. It was found that nearly all of the radioactivity was still in the 3 and 4 positions of glucose. Similarly, Lactobacillus casei formed lactic acid predominantly labeled in the carboxyl group from such glycerol. Hence the metabolism of glycerol, like that of citric acid, appears to be catalyzed by an asymmetric enzyme.