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Characterization of -Ketobutyrate Metabolism in Rat Tissues: Effects of Dietary Protein and Fasting^1,2,

Department of Nutritional Sciences, University of Wisconsin-Madison, Madison WI 53706 ^* Department of Nutrition, Rutgers University, New Brunswick, NJ 08903

The oxidative decarboxylation of -ketobutyrate was studied in rat tissue preparations. Decarboxylation was confined to the mitochondrial fraction and required coenzyme A, NAD, TPP and FAD for optimal activity in solubilized preparations. The pH optimum for this reaction in liver was 7.8, somewhat higher than that reported for other -keto acid dehydrogenases. An apparent K_m of 0.63 mM for -ketobutyrate was determined for the rat liver system. Competition by other -keto acids at 10 mM concentrations inhibited enzyme activity up to 75%. Tissue distribution of -ketobutyrate dehydrogenase activity relative to liver activity was (in percent): liver, 100; heart, 127; brain, 63; kidney, 57; skeletal muscle, 38; and small intestine, 7. Total liver -ketobutyrate dehydrogenase was decreased by 40% after a 24-hour fast. Similar results were found for kidney and heart activity. -Aminobutyratepyruvate aminotransferase activity in liver or kidney was not affected by fasting; however, it was induced in liver by 50% after feeding a 40% casein diet for 10 days compared to rats fed a 20% casein diet. Increasing the dietary casein content from 6 through 40% of the diet resulted in about a fivefold increase in liver -ketobutyrate dehydrogenase activity. The substantial extrahepatic capacity for -ketobutyrate metabolism makes it unlikely that a loss of liver function results in an inability to metabolize -ketobutyrate. Whether -ketobutyrate is decarboxylated by a specific enzyme or by an already characterized complex such as pyruvate dehydrogenase or the branched-chain keto acid dehydrogenase remains to be established.

KEY WORDS: • -aminobutyrate • -ketobutyrate • liver disease • branched-chain amino acids • keto acids

¹ This work was supported in part by U.S. Public Health Service AM32521, The Nutrition Foundation, Inc., The New Jersey Agricultural Experiment Station, and by the College of Agricultural and Life Sciences, University of Wisconsin-Madison.

² A preliminary report of this work appeared in Federation Proc. 41, 363, 1982.

Manuscript received 3 August 1983.