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Effect of Starvation and Diet Composition on Two Pathways of L-Serine Metabolism in Isolated Rat Hepatocytes¹

Department of Physiological Sciences, School of Veterinary Medicine, University of California, Davis, California 95616

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 aminotransferasemediated 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.

KEY WORDS: • serine • gluconeogenesis • serine aminotransferase • serine dehydratase

¹ Supported in part by USPHS Grant No. 04732 from the National Institutes of Health. A preliminary report of this work was presented at FASEB meeting, April 1980 in Anaheim, CA.

² Present address is: Gale P. Beliveau, Miami Valley Laboratories, Procter and Gamble Co., P.O. Box 39175, Cincinnati, Ohio 45247.

³ To whom reprint requests should be sent.

Manuscript received 24 June 1981.