Thiol methyltransferase activity in inflammatory bowel disease

Abstract

Background-Luminal anionic sulphide may contribute to epithelial damage in ulcerative colitis. Thiol methyltransferase (TMT) governs sulphide detoxification by the colonic mucosa and circulating erythrocytes. Aims-To measure levels of TMT activity in erythrocytes of surgically treated cases of colitis or in rectal biopsies of defined groups of colitis. Patients-Venepuncture blood was obtained from 37 blood donors and 27 subjects who had previously undergone a proctocolectomy for colitis: 18 for ulcerative colitis and nine for Crohn's colitis. Rectal biopsies from 122 cases were obtained: 47 without mucosal disease, 33 post-colon resection for cancer, 14 with moderate to severe ulcerative colitis, 15 with quiescent ulcerative colitis, seven with acute Crohn's colitis, and six with radiation proctitis. Methods-TMT activity was measured by high performance liquid chromatography with radioactive detection to measure 14 C methylmercaptoethanol formation, the reaction product of cell extracts incubated with mercaptoethanol and 14 C S-adenosylmethionine. Results-Erythrocyte TMT activity of surgically treated cases of colitis was significantly elevated (p<0.001) compared with control cases. TMT activity of rectal biopsies was significantly decreased (p<0.02) in acute but not quiescent ulcerative colitis, Crohn's colitis, or radiation colitis. Conclusions-Erythrocyte TMT activity was persistently elevated after proctocolectomy for Crohn's disease and ulcerative colitis. No primary defect of TMT activity was found in any case of unoperated colitis but mucosal activity was diminished with disease progression of ulcerative colitis. Studies of genetic control of TMT activity of erythrocytes in inflammatory bowel disease appear worthwhile.

Impaired Detoxication of Hydrogen Sulfide in Ulcerative Colitis?

“…We did, however, find that RHOD activity in erythrocytes was significantly higher in UC (but not in CD) patients than in community controls or Hcontrols. Similar results were obtained for TMT, which is in agreement with the findings of Roediger and Babidge [22] and Pitcher et al [23]. Roediger and Babidge found higher levels of TMT in CD also, which we did not.…”

Antioxidants as novel therapy in a murine model of colitis

“…In the human colon, methylation appears to protect colonic epithelial cells against sulfide-induced inhibition of n-butyrate oxidation. This action cannot be directly correlated with mucosal TMT activity [35].…”

Mucosal protection against sulphide: importance of the enzyme rhodanese

“…18 We found that in human colonic homogenates, a similar level of RHOD enzyme activity exists at physiological concentrations of H 2 S (1-2 mM), substantiating the claim that this enzyme may be the in vivo detoxifier of H 2 S. 18 Levitt and colleagues 18 have demonstrated radiolabelled H 2 S removal in rat caecal blood and have shown that the TMT transmethylation reaction is not involved, in contrast with data recently reported using 2-mercaptoethanol as substrate. 19 Our studies indicate that RHOD is likely to be the responsible enzyme for detoxification of H 2 S. In vivo, data to date have focused on the role of RHOD as a detoxifier of cyanide and not on the role proposed here, as a detoxifier of H 2 S. The source of the cyanide cosubstrate is unknown but we found that prevailing levels of thiocyanate are high in plasma (0.19 mM in non-smokers and 0.32 mM in smokers), indicating that there is an ample source of cyanide available to act as cosubstrate in the proposed reaction.…”