Major pathways of glycine and serine catabolism in rat liver

Abstract

The metabolism of glycine and serine in rat liver was studied with mitochondria, cell homogenates and liver slices. It was shown that the most significant pathway of glycine catabolism in rat liver is the direct cleavage of glycine to form methylene-THF, CO 2and ammonia, followed by the further oxidation of methylene-THF to CO 2, possibly by the sequential action of methylene-THF dehydrogenase, cyclohydrolase and 10-formyl-THF: NADP + oxidoreductase in liver mitochondria. Liver mitochondria, as well as liver homogenates and liver slices, actively catabolized serine and the patterns of serine catabolism in the liver homogenate and liver slice systems were essentially similar to those observed with liver mitochondria. A greater amount of 14CO 2 was obtained from serine-3- 14C than from serine-1- 14C in any system tested, and this difference was more distinct when relatively low concentrations of serine were employed. In the liver homogenate system, as well as in the liver slice system, the rate of 14CO 2 formation from serine-3- 14C was much higher than that from pyruvate-3- 14C. However, the activity of serine catabolism in the homogenate system was somewhat higher than in the mitochondrial system, although the soluble fraction alone catalyzed very little 14CO 2 formation from either serine-1- 14C or -3- 14C. In the homogenate system, the β-carbon of serine was converted to CO 2 even more rapidly than the carboxyl carbon of glycine. This seemed to be due to the participation of serine hydroxymethyltransferase, methylene-THF dehydrogenase and other enzymes related to one-carbon metabolism in the soluble liver fraction; these enzymes would increase the production of glycine, as well as the conversion of the β-carbon of serine to some one-carbon compound which may be oxidized to CO 2 in mitochondria. It was assumed that serine catabolism in liver under physiological conditions would proceed mainly by way of preliminary cleavage to methylene-THF and glycine and their subsequent oxidation to yield CO 2 as the final product in mitochondria. Serine can also be catabolized by serine dehydratase in the soluble liver fraction and through other minor pathways.