Abstract
L-Serine metabolism in rabbit, dog, and human livers was investigated, focusing on the relative contributions of the three pathways, one initiated by serine dehydratase, another by serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT), and the other involving serine hydroxymethyltransferase and the mitochondrial glycine cleavage enzyme system (GCS). Under quasi-physiological in vitro conditions (1 mM L-serine and 0.25 mM pyruvate), flux through serine dehydratase accounted for only traces, and that through SPT/AGT substantially contributed no matter whether the enzyme was located in peroxisomes (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 decarboxylation 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 with that through SPT/AGT. An in vivo experiment with L-[3-3H,14C]serine as the substrate indicated that in rabbit liver, gluconeogenesis from L-serine proceeds mainly via hydroxypyruvate. Because an important role in the conversion of glyoxylate to glycine has been assigned to peroxisomal SPT/AGT from the studies on primary hyperoxaluria type 1, these results suggest that SPT/AGT in this organelle plays dual roles in the metabolism of glyoxylate and serine.
Highlights
L-Serine metabolism in rabbit, dog, and human livers was investigated, focusing on the relative contributions of the three pathways, one initiated by serine dehydratase, another by serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT), and the other involving serine hydroxymethyltransferase and the mitochondrial glycine cleavage enzyme system (GCS)
We have presented in vitro and in vivo data suggesting that, in rabbit, dog, and human livers, SPT/AGT substantially contributes to the metabolism of L-serine, whereas the contribution of serine dehydratase (SDH) is fairly small
This pattern of L-serine metabolism is in contrast to the observation that in rat liver the contribution of SDH is the largest, and the flux through SPT/AGT accounts for only traces unless this enzyme has been induced by a previous administration of glucagon (7)
Summary
Materials—Sources of all reagents and male Wistar rats are described in the preceding paper (7). Japanese white male rabbits weighing ϳ2 kg were obtained from a local dealer. Small pieces of human livers were obtained at the time of surgical operation (hepatic left lobectomy) on three patients who suffered from biliary tract carcinoma or liver metastasis of a sarcoma. Use of the liver samples from human subjects in this study was permitted by the Ethical Committee of Hamamatsu University School of Medicine, and the patients consented to use of the resected specimens. Small pieces of human liver specimens were obtained on autopsy ϳ5 h postmortem. The SPT activity of SPT/AGT in rat, rabbit, and dog livers was determined using the cytoplasmic extract (650 ϫ g supernatant). For determination of the SPT activity in human liver, small pieces of liver specimens obtained on autopsy ϳ5 h postmortem were homogenized, and the 600 ϫ g supernatants from sonicated homogenates were subjected to the assay.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
