Sulphide impairment of substrate oxidation in rat colonocytes: a biochemical basis for ulcerative colitis?

Abstract

1. Isolated colonic epithelial cells of the rat were incubated for 40 min with [6-14C]glucose and n-[1-14C]butyrate in the presence of 0.1-2.0 mmol/l NaHS, a concentration range found in the human colon. Metabolic products, 14CO2, acetoacetate, beta-hydroxybutyrate and lactate, were measured and injury to cells was judged by diminished production of metabolites. 2. Oxidation of n-butyrate to CO2 and acetoacetate was reduced at 0.1 and 0.5 mmol/l NaHS, whereas glucose oxidation remained unimpaired. At 1.0-2.0 mmol/l NaHS, n-butyrate and glucose oxidation were dose-dependently reduced at the same rate. 3. To bypass short-chain acyl-CoA dehydrogenase activity necessary for butyrate oxidation, ketogenesis from crotonate was measured in the presence of 1.0 mmol/l NaHS. Suppression by sulphide of ketogenesis from crotonate (-10.5 +/- 6.1%) compared with control conditions was not significant, whereas suppression of ketogenesis from n-butyrate (-36.00 +/- 5.14%) was significant (P = < 0.01). Inhibition of FAD-linked oxidation was more affected by NaHS than was NAD-linked oxidation. 4. L-Methionine (5.0 mmol/l) significantly redressed the impaired beta-oxidation induced by NaHS. Methionine equally improved CO2 and ketone body production, suggesting a global reversal of the action of sulphide. 5. Sulphide-induced oxidative changes closely mirror the impairment of beta-oxidation observed in colonocytes of patients with ulcerative colitis. A hypothesis for the disease process of ulcerative colitis is that sulphides may form persulphides with butyryl-CoA, which would inhibit cellular short-chain acyl-CoA deHydrogenase and beta-oxidation to induce an energy-deficiency state in colonocytes and mucosal inflammation.

• Authors: W E Roediger, A Duncan, O Kapaniris, S Millard
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 85 Issue 5 Pg. 623-7 (Nov 1993) ISSN: 0143-5221 [Print] England
• PMID: 8287651 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Butyrates
• Ketone Bodies
• Sulfides
• Butyric Acid
• Carbon Dioxide
• Methionine
• sodium bisulfide
• Glucose

Topics

• Animals
• Butyrates (metabolism)
• Butyric Acid
• Carbon Dioxide (metabolism)
• Colitis, Ulcerative (metabolism)
• Colon (metabolism)
• Glucose (metabolism)
• Ketone Bodies (metabolism)
• Male
• Methionine (metabolism)
• Oxidation-Reduction
• Rats
• Sulfides (metabolism)