Kinetics of butyrate metabolism in the normal colon and in ulcerative colitis: the effects of substrate concentration and carnitine on the β-oxidation pathway

Abstract

Butyrate, a colonic metabolite of carbohydrates, is considered as the major energy source for the colonic mucosa. An impaired butyrate metabolism has been reported in ulcerative colitis (UC), however, the cause still remains unknown. In the present study, we investigated whether higher butyrate concentrations could normalise the oxidation rate in UC. Furthermore, it was investigated whether carnitine could enhance the butyrate oxidation. Mucosal biopsies from a total of 26 UC patients and 25 controls were incubated with (14)C-labelled Na-butyrate and the produced (14)CO(2) was measured. First, the rate of oxidative metabolism was compared at three different concentrations of Na-butyrate (0.05 mm, 1 mm and 10 mm). Then, incubations of biopsies were performed with carnitine alone or combined with ATP. Overall, butyrate oxidation in UC was significantly lower than that in controls. The maximum rate of butyrate oxidation was achieved in UC and control subjects from 1 mm onwards. Increasing the butyrate concentration to a level to be present in the colonic lumen, i.e. 10 mm, did not increase the rate of butyrate oxidation in UC to the rate observed in controls. Addition of carnitine alone or combined with ATP caused no effects. Saturation of butyrate kinetics was achieved from 1 mm in UC and control subjects. The rate of butyrate metabolism was significantly impaired in active ulcerative colitis. The addition of compounds interfering with the β-oxidation pathway had no effect on the butyrate metabolism in UC.