CATABOLISM OF ISOBUTYRATE BY COLONOCYTES

Isolated colonocytes have more capacity for the oxidation of isobutyra te and alpha-ketoisovalerate than isolated enterocytes. Both enterocyt es and colonocytes express high levels of 3-hydroxyisobutyryl-CoA hydr olase, an enzyme activity important in maintaining low intracellular c oncentrations of methacrylyl-CoA, a common, potentially toxic intermed iate in the catabolic pathways of these compounds. In spite of compara ble 3-hydroxyisobutyryl-CoA hydrolase activities in both cell types, a nd much greater amounts of 3-hydroxyisobutyrate dehydrogenase in colon ocytes than in enterocytes, only the colonocytes produced 3-hydroxyiso butyrate as an endproduct of alpha-ketoisovalerate and isobutyrate cat abolism. Butyrate very effectively inhibits isobutyrate catabolism by colonocytes, most likely by competitively inhibiting activation of iso butyrate to its CoA ester, Oleate also inhibits isobutyrate catabolism , but at a site more distal than butyrate. Starvation of rats for 72 h decreased the capacity of colonocytes for butyrate but not isobutyrat e catabolism, We conclude that isobutyrate could function as a carbon source for energy and anapleurosis in colonocytes under conditions of defective butyrate oxidation or low butyrate availability. (C) 1996 Ac ademic Press, Inc.