Skip to main content
Gut logoLink to Gut
. 1996 Jul;39(1):77–81. doi: 10.1136/gut.39.1.77

Methionine derivatives diminish sulphide damage to colonocytes--implications for ulcerative colitis.

W E Roediger 1, W Babidge 1, S Millard 1
PMCID: PMC1383236  PMID: 8881814

Abstract

BACKGROUND: Bacterial production of anionic sulphide is increased in the colon of ulcerative colitis and sulphides can cause metabolic damage to colonocytes. AIMS: To assess the reversal of the damaging effect of sulphide to isolated colonocytes by methionine and methionine derivatives. METHODS AND SUBJECTS: Isolated colonocytes were prepared from rat colons and 12 human colectomy specimens. In cell suspensions 14CO2/acetoacetate generation was measured from [1-14C]-butyrate (5.0 mmol/l) in the presence of 0-2.0 mmol/l sodium hydrogen sulphide. The effect of 5.0 mmol/l L-methionine, S-adenosylmethionine 1,4 butane disulphonate and DL-methionine-S-methylsulphonium chloride on sulphide inhibited oxidation was observed. RESULTS: In rat colonocytes sodium hydrogen sulphide dose dependently reduced oxidative metabolite formation from n-butyrate, an action reversed in order of efficacy by S-adenosylmethionine 1,4 butane disulphonate > DLmethionine-S-methyl-sulphonium chloride > L-methionine. In human colonocytes S-adenosylmethionine 1,4 butane disulphonate most significantly improved 14CO2 production (p = < 0.005) suppressed by sodium hydrogen sulphide. CONCLUSION: Sulphide toxicity in colonocytes is reversible by methyl donors. The efficiency of sulphide detoxification may be an important factor in the pathogenesis and treatment of ulcerative colitis for which S-adenosylmethionine 1,4 butane disulphonate may be of therapeutic value.

Full text

PDF
77

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahlman B., Leijonmarck C. E., Lind C., Vinnars E., Wernerman J. Free amino acids in biopsy specimens from the human colonic mucosa. J Surg Res. 1993 Dec;55(6):647–653. doi: 10.1006/jsre.1993.1198. [DOI] [PubMed] [Google Scholar]
  2. Bray T. M., Taylor C. G. Enhancement of tissue glutathione for antioxidant and immune functions in malnutrition. Biochem Pharmacol. 1994 Jun 15;47(12):2113–2123. doi: 10.1016/0006-2952(94)90246-1. [DOI] [PubMed] [Google Scholar]
  3. Brown M. D., Dudeja P. K., Brasitus T. A. S-adenosyl-L-methionine modulates Na+ + K+-ATPase activity in rat colonic basolateral membranes. Biochem J. 1988 Apr 1;251(1):215–222. doi: 10.1042/bj2510215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chawla R. K., Bonkovsky H. L., Galambos J. T. Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease. Drugs. 1990;40 (Suppl 3):98–110. doi: 10.2165/00003495-199000403-00010. [DOI] [PubMed] [Google Scholar]
  5. Cooper A. J. Biochemistry of sulfur-containing amino acids. Annu Rev Biochem. 1983;52:187–222. doi: 10.1146/annurev.bi.52.070183.001155. [DOI] [PubMed] [Google Scholar]
  6. Dahm L. J., Jones D. P. Secretion of cysteine and glutathione from mucosa to lumen in rat small intestine. Am J Physiol. 1994 Aug;267(2 Pt 1):G292–G300. doi: 10.1152/ajpgi.1994.267.2.G292. [DOI] [PubMed] [Google Scholar]
  7. Darragh A. J., Cranwell P. D., Moughan P. J. Absorption of lysine and methionine from the proximal colon of the piglet. Br J Nutr. 1994 May;71(5):739–752. doi: 10.1079/bjn19940181. [DOI] [PubMed] [Google Scholar]
  8. Eloranta T. O. Tissue distribution of S-adenosylmethionine and S-adenosylhomocysteine in the rat. Effect of age, sex and methionine administration on the metabolism of S-adenosylmethionine, S-adenosylhomocysteine and polyamines. Biochem J. 1977 Sep 15;166(3):521–529. doi: 10.1042/bj1660521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Florin T., Neale G., Gibson G. R., Christl S. U., Cummings J. H. Metabolism of dietary sulphate: absorption and excretion in humans. Gut. 1991 Jul;32(7):766–773. doi: 10.1136/gut.32.7.766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Friedel H. A., Goa K. L., Benfield P. S-adenosyl-L-methionine. A review of its pharmacological properties and therapeutic potential in liver dysfunction and affective disorders in relation to its physiological role in cell metabolism. Drugs. 1989 Sep;38(3):389–416. doi: 10.2165/00003495-198938030-00004. [DOI] [PubMed] [Google Scholar]
  11. Fuchs G., Ecker A., Strauss G. Bioenergetics and autotrophic carbon metabolism of chemolithotrophic archaebacteria. Biochem Soc Symp. 1992;58:23–39. [PubMed] [Google Scholar]
  12. Garcia R. A., Stipanuk M. H. The splanchnic organs, liver and kidney have unique roles in the metabolism of sulfur amino acids and their metabolites in rats. J Nutr. 1992 Aug;122(8):1693–1701. doi: 10.1093/jn/122.8.1693. [DOI] [PubMed] [Google Scholar]
  13. Gibson G. R., Cummings J. H., Macfarlane G. T. Competition for hydrogen between sulphate-reducing bacteria and methanogenic bacteria from the human large intestine. J Appl Bacteriol. 1988 Sep;65(3):241–247. doi: 10.1111/j.1365-2672.1988.tb01891.x. [DOI] [PubMed] [Google Scholar]
  14. Gibson G. R., Macfarlane G. T., Cummings J. H. Occurrence of sulphate-reducing bacteria in human faeces and the relationship of dissimilatory sulphate reduction to methanogenesis in the large gut. J Appl Bacteriol. 1988 Aug;65(2):103–111. doi: 10.1111/j.1365-2672.1988.tb01498.x. [DOI] [PubMed] [Google Scholar]
  15. Gibson G. R., Macfarlane G. T., Cummings J. H. Sulphate reducing bacteria and hydrogen metabolism in the human large intestine. Gut. 1993 Apr;34(4):437–439. doi: 10.1136/gut.34.4.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hegarty R. S., Nolan J. V., Leng R. A. Sulphur availability and microbial fermentation in the fauna-free rumen. Arch Tierernahr. 1991 Oct;41(7-8):725–736. doi: 10.1080/17450399109428517. [DOI] [PubMed] [Google Scholar]
  17. Ishioka T., Kuwabara N., Oohashi Y., Wakabayashi K. Induction of colorectal tumors in rats by sulfated polysaccharides. Crit Rev Toxicol. 1987;17(3):215–244. doi: 10.3109/10408448709071209. [DOI] [PubMed] [Google Scholar]
  18. JENNINGS M. A., FLOREY H. W. Autoradiographic observations on the mucous cells of the stomach and intestine. Q J Exp Physiol Cogn Med Sci. 1956 Apr;41(2):131–152. doi: 10.1113/expphysiol.1956.sp001171. [DOI] [PubMed] [Google Scholar]
  19. Kameyama J., Narui H., Inui M., Sato T. Energy level in large intestinal mucosa in patients with ulcerative colitis. Tohoku J Exp Med. 1984 Jun;143(2):253–254. doi: 10.1620/tjem.143.253. [DOI] [PubMed] [Google Scholar]
  20. Kelly F. J. Glutathione content of the small intestine: regulation and function. Br J Nutr. 1993 Mar;69(2):589–596. doi: 10.1079/bjn19930058. [DOI] [PubMed] [Google Scholar]
  21. Lund J., Stjernström H., Vinnars E., Jorfeldt L., Bergholm U., Wiklund L. The influence of abdominal surgery on the splanchnic exchange of amino acids. Acta Chir Scand. 1986 Mar;152:191–197. [PubMed] [Google Scholar]
  22. Mårtensson J., Jain A., Meister A. Glutathione is required for intestinal function. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1715–1719. doi: 10.1073/pnas.87.5.1715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pacifici G. M., Romiti P., Santerini S., Giuliani L. S-methyltransferases in human intestine: differential distribution of the microsomal thiol methyltransferase and cytosolic thiopurine methyltransferase along the human bowel. Xenobiotica. 1993 Jun;23(6):671–679. doi: 10.3109/00498259309059404. [DOI] [PubMed] [Google Scholar]
  24. Pochart P., Doré J., Lémann F., Goderel I., Rambaud J. C. Interrelations between populations of methanogenic archaea and sulfate-reducing bacteria in the human colon. FEMS Microbiol Lett. 1992 Nov 1;77(1-3):225–228. doi: 10.1016/0378-1097(92)90160-p. [DOI] [PubMed] [Google Scholar]
  25. Rao A. M., Drake M. R., Stipanuk M. H. Role of the transsulfuration pathway and of gamma-cystathionase activity in the formation of cysteine and sulfate from methionine in rat hepatocytes. J Nutr. 1990 Aug;120(8):837–845. doi: 10.1093/jn/120.8.837. [DOI] [PubMed] [Google Scholar]
  26. Roediger W. E., Duncan A., Kapaniris O., Millard S. Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis. Gastroenterology. 1993 Mar;104(3):802–809. doi: 10.1016/0016-5085(93)91016-b. [DOI] [PubMed] [Google Scholar]
  27. Roediger W. E., Duncan A., Kapaniris O., Millard S. Sulphide impairment of substrate oxidation in rat colonocytes: a biochemical basis for ulcerative colitis? Clin Sci (Lond) 1993 Nov;85(5):623–627. doi: 10.1042/cs0850623. [DOI] [PubMed] [Google Scholar]
  28. Roediger W. E. Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut. 1980 Sep;21(9):793–798. doi: 10.1136/gut.21.9.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Roediger W. E. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology. 1982 Aug;83(2):424–429. [PubMed] [Google Scholar]
  30. Salim A. S. Role of sulphydryl-containing agents in the management of recurrent attacks of ulcerative colitis. A new approach. Pharmacology. 1992;45(6):307–318. doi: 10.1159/000139016. [DOI] [PubMed] [Google Scholar]
  31. Strocchi A., Ellis C. J., Furne J. K., Levitt M. D. Study of constancy of hydrogen-consuming flora of human colon. Dig Dis Sci. 1994 Mar;39(3):494–497. doi: 10.1007/BF02088333. [DOI] [PubMed] [Google Scholar]
  32. Strocchi A., Furne J., Ellis C., Levitt M. D. Methanogens outcompete sulphate reducing bacteria for H2 in the human colon. Gut. 1994 Aug;35(8):1098–1101. doi: 10.1136/gut.35.8.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weisiger R. A., Pinkus L. M., Jakoby W. B. Thiol S-methyltransferase: suggested role in detoxication of intestinal hydrogen sulfide. Biochem Pharmacol. 1980 Oct 15;29(20):2885–2887. doi: 10.1016/0006-2952(80)90029-5. [DOI] [PubMed] [Google Scholar]
  34. di Padova C. S-adenosylmethionine in the treatment of osteoarthritis. Review of the clinical studies. Am J Med. 1987 Nov 20;83(5A):60–65. doi: 10.1016/0002-9343(87)90853-9. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES