SULFIDES IMPAIR SHORT-CHAIN FATTY-ACID BETA-OXIDATION AT ACYL-COA DEHYDROGENASE LEVEL IN COLONOCYTES - IMPLICATIONS FOR ULCERATIVE-COLITIS

The disease process of ulcerative colitis (UC) is associated with a bl ock in beta-oxidation of short chain fatty acid in colonic epithelial cells which can be reproduced by exposure of cells to sulfides. The ai m of the current work was to assess the level in the beta-oxidation pa thway at which sulfides might be inhibitory in human colonocytes. Isol ated human colonocytes from cases without colitis (n = 12) were expose d to sulfide (1.5 mM) in the presence or absence of exogenous CoA and ATP. Short chain acyl-CoA esters were measured by a high performance l iquid chromatographic assay. (CO2)-C-14 generation was measured from [ 1-C-14]butyrate and [6-C-14]glucose. (CO2)-C-14 from butyrate was sign ificantly reduced (p < 0.001) by sulfide. When colonocytes were incuba ted with hydrogen sulfide in the presence of CoA and ATP, butyryl-CoA concentration was increased (p < 0.01), while crotonyl-CoA (p < 0.01) and acetyl-CoA (p < 0.01) concentrations were decreased. These results show that sulfides inhibit short chain acyl-CoA dehydrogenase. As oxi dation of n-butyrate governs the epithelial barrier function of colono cytes the functional activity of short chain acyl-CoA dehydrogenase ma y be critical in maintaining colonic mucosal integrity. Maintaining th e functional activity of dehydrogenases could be an important determin ant in the expression of ulcerative colitis.