Flux of the L-serine metabolism in rat liver - The predominant contribution of serine dehydratase

L-Serine metabolism in rat liver was investigated, focusing on the relative contributions of the three pathways, one initiated by L-serine dehydratase (SDR), another by serine: pyruvate/alanine:glyoxylate aminotransferase (SP T/AGT), and the other involving serine hydroxymethyltransferase and the mit ochondrial glycine cleavage enzyme system (GCS). Because serine hydroxymeth yltransferase is responsible for the interconversion between serine and gly cine, SDH, SPT/AGT, and GCS were considered to be the metabolic exits of th e serine-glycine pool. In vitro, flux through SDH was predominant in both 2 4-h starved and glucagon-treated rats. Flux through SPT/AGT was enhanced by glucagon administration, but even after the induction, its contribution un der quasi-physiological conditions (1 mM L-serine and 0.25 mM pyruvate) was about 1/10 of that through SDH. Flux through GCS accounted for only severa l percent of the amount of L-serine metabolized. Relative contributions of SDH and SPT/AGT to gluconeogenesis from L-serine were evaluated in vivo bas ed on the principle that H-3 at the 3 position of L-serine is mostly remove d in the SDH pathway, whereas it is largely retained in the SPT/AGT pathway . The results showed that SPT/AGT contributed only 10-20% even after the en hancement of its activity by glucagon. These results suggested that SDH is the major metabolic exit of L-serine in rat liver.