W. Babidge et al., SULFIDES IMPAIR SHORT-CHAIN FATTY-ACID BETA-OXIDATION AT ACYL-COA DEHYDROGENASE LEVEL IN COLONOCYTES - IMPLICATIONS FOR ULCERATIVE-COLITIS, Molecular and cellular biochemistry, 181(1-2), 1998, pp. 117-124
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.