Abstract
L-Serine metabolism in rat liver was investigated, focusing on the relative contributions of the three pathways, one initiated by L-serine dehydratase (SDH), another by serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT), and the other involving serine hydroxymethyltransferase and the mitochondrial glycine cleavage enzyme system (GCS). Because serine hydroxymethyltransferase is responsible for the interconversion between serine and glycine, SDH, SPT/AGT, and GCS were considered to be the metabolic exits of the serine-glycine pool. In vitro, flux through SDH was predominant in both 24-h starved and glucagon-treated rats. Flux through SPT/AGT was enhanced by glucagon administration, but even after the induction, its contribution under 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 several percent of the amount of L-serine metabolized. Relative contributions of SDH and SPT/AGT to gluconeogenesis from L-serine were evaluated in vivo based on the principle that 3H at the 3 position of L-serine is mostly removed 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 enhancement of its activity by glucagon. These results suggested that SDH is the major metabolic exit of L-serine in rat liver.
Highlights
L-Serine metabolism in rat liver was investigated, focusing on the relative contributions of the three pathways, one initiated by L-serine dehydratase (SDH), another by serine: pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT), and the other involving serine hydroxymethyltransferase and the mitochondrial glycine cleavage enzyme system (GCS)
Relative contributions of SDH and SPT/AGT to gluconeogenesis from L-serine were evaluated in vivo based on the principle that 3H at the 3 position of L-serine is mostly removed in the SDH pathway, whereas it is largely retained in the SPT/AGT pathway
It has been established that three pathways are involved in the metabolism of L-serine: 1) that catalyzed by serine hydroxymethyltransferase (SHMT),1 which is responsible for the reversible conversion of L-serine
Summary
(Received for publication, December 23, 1998, and in revised form, March 2, 1999). Hai-Hui Xue‡§, Michio Fujie¶, Takanori Sakaguchiʈ, Toshiaki Oda‡, Hirofumi Ogawa**, Nancy M. L-Serine metabolism in rat liver was investigated, focusing on the relative contributions of the three pathways, one initiated by L-serine dehydratase (SDH), another by serine: pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT), and the other involving serine hydroxymethyltransferase and the mitochondrial glycine cleavage enzyme system (GCS). SHMT exists in some eukaryotic cells, including hepatocytes, as distinct isozymes, one located in the cytosol and the other in mitochondria (referred to as cSHMT and mSHMT, respectively) [2] As for their physiological functions in the liver and kidney, mSHMT has been proposed to be coupled with GCS in the conversion of glycine to serine, using 5,10-methylene-THF formed by the latter enzyme and regenerating THF [2, 4]. The metabolism of L-serine in the livers of other animal species will be described in an accompanying paper
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