Flux of the L-serine metabolism in rabbit, human, and dog livers - Substantial contributions of both mitochondrial and peroxisomal serine : pyruvate/alanine : glyoxylate aminotransferase

L-Serine metabolism in rabbit, dog, and human livers was investigated, focu sing on the relative contributions of the three pathways, one initiated by serine dehydratase, another by serine:pyruvate/alanine:glyoxylate aminotran sferase (SPT/AGT), and the other involving serine hydroxymethyltransferase and the mitochondrial glycine cleavage enzyme system (GCS), Under quasi-phy siological in vitro conditions (1 mM L-serine and 0.25 mar pyruvate), flux through serine dehydratase accounted for only traces, and that through SPT/ AGT substantially contributed no matter whether the enzyme was located in p eroxisomes (rabbit and human) or largely in mitochondria (dog), As for flux through serine hydroxymethyltransferase and GCS, the conversion of serine to glycine occurred fairly rapidly, followed by GCS-mediated slow decarboxy lation of the accumulated glycine, The flux through GCS was relatively high in the dog and low in the rabbit, and only in the dog was it comparable wi th that through SPT/AGT, An in vivo experiment with L-[3-H-3,C-14]serine as the substrate indicated that in rabbit liver, gluconeogenesis from Lserine proceeds mainly via hydroxypyruvate, Because an important role in the conv ersion of glyoxylate to glycine has been assigned to peroxisomal SPT/AGT fr om the studies on primary hyperoxaluria type I, these results suggest that SPT/AGT in this organelle plays dual roles in the metabolism of glyoxylate and serine.