title: Catabolism of isobutyrate by colonocytes.
abstract: Isolated colonocytes have more capacity for the oxidation of isobutyrate and alpha-ketoisovalerate than isolated enterocytes. Both enterocytes and colonocytes express high levels of 3-hydroxyisobutyryl-CoA hydrolase, an enzyme activity important in maintaining low intracellular concentrations of methacrylyl-CoA, a common, potentially toxic intermediate in the catabolic pathways of these compounds. In spite of comparable 3-hydroxyisobutyryl-CoA hydrolase activities in both cell types, and much greater amounts of 3-hydroxyisobutyrate dehydrogenase in colonocytes than in enterocytes, only the colonocytes produced 3-hydroxyisobutyrate as an endproduct of alpha-ketoisovalerate and isobutyrate catabolism. Butyrate very effectively inhibits isobutyrate catabolism by colonocytes, most likely by competitively inhibiting activation of isobutyrate 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 isobutyrate 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, 46202-5122, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jaskiewicz
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: J W
authors.initials: JW
authors.lastname: Hawes
authors.forename: Y
authors.initials: Y
authors.lastname: Shimomura
authors.forename: D W
authors.initials: DW
authors.lastname: Crabb
authors.forename: R A
authors.initials: RA
authors.lastname: Harris
mesh_terms: D000818:Animals; D002087:Butyrates / Q000378:metabolism*; D020148:Butyric Acid; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D058610:Isobutyrates; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D011865:Radioisotope Dilution Technique; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity; D013869:Thiolester Hydrolases / Q000378:metabolism
chemical_list: D002087:Butyrates; D002250:Carbon Radioisotopes; D058610:Isobutyrates; D020148:Butyric Acid; C020380:isobutyric acid; D013869:Thiolester Hydrolases; C035908:3-hydroxyisobutyryl-CoA hydrolase; D005947:Glucose