Dietary and Hormonal Regulation of Hepatic Biosynthetic and Catabolic Enzymes of Serine Metabolism in Rats1

The changes in the hepatic levels of activity of 3-P-glycerate dehydrogenase, D-glycerate dehydrogenase, L-serine: pyruvate transaminase and L-serine dehydratase have been determined in rats under varying conditions promoting either gluconeogenesis or amino acid biosynthesis. In the gluconeogenic states brought about by fasting, by administration of either cortisone, glucagon, or N6,O2′-dibutyryl cyclic adenosine-3′,5′-monophosphate (DBcAMP), and by alloxan diabetes, serine dehydratase activity was elevated. In the latter condition, insulin was effective in reducing the elevated level of activity. The level of serine: pyruvate transaminase activity was also increased by all of the above conditions except fasting, although the magnitude of the response and the time required to elicit a change varied from those observed for serine dehydratase. The glucagonmediated elevation of the levels of activity of both enzymes occurred independently of glucocorticoids. The level of activity of D-glycerate dehydrogenase, which utilizes hydroxypyruvate, one product of the serine: pyruvate transaminase v reaction, increased only slightly with prolonged fasting or with extended glucagon administration; this enzyme activity was diminished in cortisone injected rats. The level of activity of 3-P-glycerate dehydrogenase, a key enzyme in serine biosynthesis, was substantially decreased by all of the conditions investigated except with exogenous DBcAMP or glucagon where a significant reduction in activity was not observed. The greatly reduced level of activity of this enzyme in the diabetic animal could be restored by insulin injection. Although the present studies are suggestive that in rat liver serine: pyruvate transaminase and Dglycerate dehydrogenase may have a gluconeogenic role, not all of the results are consistent with this proposal. On the other hand, the results indicate that 3-P-glycerate dehydrogenase, the first enzyme in the biosynthetic route of serine from phosphorylated intermediates, is suppressed under gluconeogenic conditions. (Endocrinology91: 1054, 1972)