Comparative study on major pathways of glycine and serine catabolism in vertebrate livers.

Abstract

The metabolism of glycine and serine in the liver of various species of vertebrates including mammals, birds, reptiles, amphibians, and fishes was studied using mitochondria and cell homogenates. It was shown that the most significant pathway of glycine catabolism in the liver of these animals is the direct cleavage of glycine to form methylene-tetrahydrofolate (methylene-THF), CO2, and ammonia in mitochondria. Methylene-THF derived from the α-carbon of glycine can be further oxidized to CO2. Liver homogenates as well as liver mitochondria from all the animals tested also catalyzed 14CO2 formation from either serine-l-14C or -3-14C. Moreover, with ureotelic and ammonotelic animals, the soluble liver fraction alone could also oxidize the β-carbon of serine to CO2, indicating the possible occurrence of 10-formyl-THF: NADP+ oxidoreductase in both mitochondrial and soluble liver fractions. However, the soluble liver fraction of uricotelic animals such as a bird and a snake was apparently devoid of 10-formyl-THF: NADP+ oxidoreductase. With all the animals tested, both the mitochondrial and soluble liver fractions contained considerable activities of serine hydroxymethyltransferase [EC 2.1.2.1], methylene-THF dehydrogenase [EC 1.5.1.5], and methylene-THF cyclohydrolase [EC 3.5.4.9], whereas the activity of serine dehydratase [EC 4.2.1.13] was relatively low and in some animal species it was hardly detectable. It was assumed that under physiological conditions serine catabolism in vertebrate livers would proceed mainly by way of the cleavage of serine to form methylene-THF and glycine. In ureotelic and ammonotelic animal livers, methylene-THF derived from the β-carbon of serine as well as the a-carbon of glycine is further oxidized to CO2 in either the soluble fraction or mitochondria, but in uricotelic animal livers methylene-THF would be utilized mainly for purine synthesis.