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 (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.
Xue
H H
HH
First Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, Japan.
Fujie
M
M
Sakaguchi
T
T
Oda
T
T
Ogawa
H
H
Kneer
N M
NM
Lardy
H A
HA
Ichiyama
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002244:Carbon / Q000378:metabolism; D005943:Gluconeogenesis; D006859:Hydrogen / Q000378:metabolism; D066298:In Vitro Techniques; D012695:L-Serine Dehydratase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000378:metabolism*
D012694:Serine; D002244:Carbon; D006859:Hydrogen; D000255:Adenosine Triphosphate; D012695:L-Serine Dehydratase; D008274:Magnesium