Quantification of the essential methyl-group donor S-adenosyl-methionine in human colorectal mucosa of patients with inflammatory bowel disease (IBD) and colorectal adenomas

Thiede, C.; Bayerdörffer, Ekkehard; Thiede, Hans Michael; Ochsenkühn, Thomas; Neubauer, A.

doi:10.1016/0016-5085(95)26496-5

Cited by 4 publications

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“…The state of TMT activity does not however entirely reflect the capacity to methylate as the process is dependent on a supply of SAM which in the assay was exogenously provided. In UC levels of endogenous SAM are low in colonocytes40 and methylation of DNA, which is also dependent on endogenous SAM, is low in the mucosa of UC 41. The potential for sulphide to cause mucosal metabolic damage is most likely to occur later in the development of the disease process of UC when production rates of sulphide may exceed the capacity of epithelial cells to detoxify the amount of sulphide produced in the colon.…”

Section: Discussionmentioning

confidence: 99%

Thiol methyltransferase activity in inflammatory bowel disease

Roediger

2000

Gut

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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.

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Section: Discussionmentioning

confidence: 99%

Thiol methyltransferase activity in inflammatory bowel disease

Roediger

2000

Gut

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“…Distinction between erythrocyte, colonocyte and inflammatory cell activity of TMT in the colonic mucosa is important and needs to be considered in the disease process of ulcerative colitis. The concentration of the high energy cofactor S-adenosyl methionine, needed for TMT activity in colonocytes, is reduced in ulcerative colitis,81suggesting a failure of capacity to detoxify sulphide by methylation. DNA hypomethylation has also been observed in ulcerative colitis 82…”

Section: Methylation and Methyltransferasesmentioning

confidence: 99%

Human colonocyte detoxification

Roediger

Babidge

1997

Gut

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Thiolmethyltransferase activity in the human colonic mucosa: Implications for ulcerative colitis

Moore

Babidge

Millard

et al. 1997

J of Gastro and Hepatol

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Ulcerative colitis is associated with a selective reduction of n-butyrate oxidation by the colonic epithelial cells although the reason for this has been unclear. Colonic epithelial cell n-butyrate oxidation can be inhibited in vitro by incubation with sulphide but the role of mucosal detoxification of sulphide in the metabolic welfare of the colonic mucosa has not been examined. This study aimed to assess the role mucosal detoxification of sulphide by thiolmethyltransferase (TMT)-mediated methylation may play in protecting the healthy colonic mucosa from the adverse effects of luminal sulphide. Colonic epithelial cell suspensions from healthy human proximal (n = 9) and distal colon (n = 10) were incubated in the presence of 14C-labelled n-butyrate (5 mmol/L) alone, butyrate plus sodium hydrogen sulphide (NaHS) (1.5 mmol/L), or butyrate plus NaHS plus S-adenosyl-methionine 1,4 butane disulphonate (SAMe) (5 mmol/L). Study end points were metabolic performance (14CO2 production) and mucosal TMT activity. Incubation with NaHS induced a significant inhibition of 14CO2 production compared with control incubations (P < 0.001) which was similar for proximal and distal colonic cell suspensions. S-adenosyl-methionine 1,4 butane disulphonate reversed this effect completely in proximal but not in distal cell incubations, suggesting a greater susceptibility of the distal colon to the sulphide effect. Although median whole mucosal TMT values did not differ between proximal and distal colonic mucosa, a non-normal distribution of distal TMT values was observed. However, neither the degree of sulphide inhibition of control 14CO2 production nor the degree to which SAMe reversed this inhibition correlated with whole mucosal TMT activity. The study concluded that regional variation exists in TMT activity in the human colon but whilst methylation appears to protect colonic epithelial cells against sulphide-induced inhibition of n-butyrate oxidation, this cannot be directly correlated with mucosal TMT activity.

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Quantification of the essential methyl-group donor S-adenosyl-methionine in human colorectal mucosa of patients with inflammatory bowel disease (IBD) and colorectal adenomas

Cited by 4 publications

References 0 publications

Thiol methyltransferase activity in inflammatory bowel disease

Thiol methyltransferase activity in inflammatory bowel disease

Human colonocyte detoxification

Thiolmethyltransferase activity in the human colonic mucosa: Implications for ulcerative colitis

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