Effect of starvation and diet composition on two pathways of L-serine metabolism in isolated rat hepatocytes.

This study examined the effects of starvation and of feeding to rats diets that contain varying protein, carbohydrate and fat levels on serine metabolism in isolated hepatocytes. The conversion of [14C]serine and [14C]lactate to 14CO2 and [14C]glucose was measured in the presence and absence of 5 mM quinolinic acid (QA) or 1 mM 3-mercaptopicolinic acid (MPA), inhibitors of phosphoenolpyruvate carboxykinase. Inclusion of MPA eliminated the contribution of the serine dehydratase-mediated pathway of serine metabolism to glucose production, allowing estimation of serine aminotransferase-mediated metabolism. Addition of MPA reduced [14C]glucose formation from [14C]serine to between 3 and 47% of control values in all dietary treatments. Addition of 10 mM threonine or 10 mM pyruvate depressed [14C]glucose production in hepatocytes from the groups fed 80% protein. Differences in serine metabolism were observed within each protein group, depending on the carbohydrate and fat ratio of the diet. These results suggest the following: 1) MPA is a more potent gluconeogenic inhibitor than QA, permitting estimation of relative flux through two pathways of serine metabolism; 2) serine metabolism occurs primarily via serine dehydratase, although the contribution of serine aminotransferase varies depending upon the nutritional state of the rat, and 3) changing a single dietary component at the expense of another may mask the intricacies of metabolic homeostasis.