Effect of acute ethanol on serine biosynthesis in liver.
The effect of an acute intraperitoneal dose of ethanol (1 g/kg), glucose (7.2 g/kg), or the combination of the two on the metabolite pattern of the biosynthetic pathway of L-serine has been determined in rabbit liver in vivo as has the effect of 10 mM ethanol on the glucose-, fructose-, or pyruvate-stimulated accumulation of L-serine in rabbit hepatocytes in vitro. In vivo, the 50% increase in L-serine and 80% increase in L-phosphoserine content of liver following glucose injection was completely prevented by ethanol. In fact, the L-phosphoserine content fell to only 6% of the control value. In spite of these and other significant changes in the metabolite pattern of the pathway of L-serine biosynthesis (D-3-phosphoglycerate dehydrogenase, L-phosphoserine aminotransferase (PSAT), and L-phosphoserine phosphatase), the mass action ratio of the combined reactions of the first two steps remained close to their equilibrium position. As a consequence it is estimated that the tissue content of phosphohydroxypyruvate fell to less than 2% of the control value, to approximately 0.3% of its Km for the PSAT reaction. The conclusion that acute ethanol blocks L-serine biosynthesis (presumably by redox effects) was supported by the prevention or inhibition of L-serine accumulation in hepatocytes metabolizing glucose, fructose, or pyruvate. Because L-serine is an important source of one-carbon fragments, the inhibition of its biosynthesis may be another mechanism by which ethanol interferes with folate and one-carbon metabolism.
D000435:Alcoholic Intoxication / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009243:NAD / Q000378:metabolism; D011817:Rabbits; D012694:Serine / Q000096:biosynthesis*
D009243:NAD; D000431:Ethanol; D012694:Serine; D005947:Glucose