Digestive Diseases and Sciences

, Volume 48, Issue 10, pp 2083–2090 | Cite as

Homocysteine, Cysteine, and Glutathione in Human Colonic Mucosa: Elevated Levels of Homocysteine in Patients with Inflammatory Bowel Disease

  • I. MorgensternEmail author
  • M.T.M. Raijmakers
  • W.H.M. Peters
  • H. Hoensch
  • W. Kirch


The present study was performed to evaluate the levels of the amino thiols cysteine, homocysteine, and glutathione in the colonic mucosa of patients with various intestinal diseases, especially chronic inflammatory bowel disease. Colonic biopsies of macroscopically normal mucosa out of a proximal and distal segment were collected from 187 patients with various intestinal diseases. Protein was assayed in duplicate by the method of Lowry et al (1951), using bovine serum albumin as standard. Total glutathione, cysteine, and homocysteine were quantified by high performance liquid chromatography (HPLC) with fluorescent detection. Only in patients with inflammatory bowel disease were the homocysteine levels in the large bowel mucosa significantly elevated compared with the concentrations in patients with normal mucosa. No significant differences were seen for glutathione and cysteine concentrations in colonic mucosa among the different groups of diseases. No correlation was found between the age of the patients and levels of the amino thiols investigated. GSH content and concentrations of cysteine and homocysteine were similar in male and female subjects. In our study markedly elevated concentrations of homocysteine in the colonic mucosa were observed in patients suffering from ulcerative colitis and Crohn's disease. This finding has been reported already in the literature for plasma homocysteine levels. Increased homocysteine levels in the colonic mucosa and plasma of patients with inflammatory bowel disease may play a role in the pathogenesis of Crohn's disease and ulcerative colitis.

homocysteine cysteine glutathione inflammatory bowel disease 


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  1. 1.
    Peters WHM, Roelfs HMJ, Nagengast FM, et al: Human intestinal glutathione S-transferases. Biochem J 257:471-476, 1989Google Scholar
  2. 2.
    Raijmakers MTM, Zusterzeel PLM, Steegers EAP, Hectors MPC, Demacker PNM, Peters WHM: Plasma thiol status in preeclampsia. Obstet Gynecol 95:180-184, 2000Google Scholar
  3. 3.
    Finkelstein JD: Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost 26:219-225, 2000Google Scholar
  4. 4.
    Moat SJ, Bonham JR, Cragg RA, Powers HJ: Elevated plasma homocysteine elicits an increase in antioxidant enzyme activity. Free Radic Res 32:171-179, 2000Google Scholar
  5. 5.
    Selhub J, Jacques PF, Bostom AG, Dágostino RB, Wilson PF, Belanger AJ, O'Leary DH, Wolf PA, Schaefer EF, Rosenberg IH: Association between homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med 332:286-291, 1995Google Scholar
  6. 6.
    Malinow MR: Plasma homocysteine and arterial occlusive diseases: a mini-review. Clin Chem 41:173-176, 1995Google Scholar
  7. 7.
    Moghadasian MH, McManus BM, Frohlich JJ: Homocysteine and coronary artery disease. Clinical evidence and genetic and metabolic background. Arch Intern Med 157:2299-2308, 1997Google Scholar
  8. 8.
    Langman LJ, Cole DE: Homocysteine. Crit Rev Clin Lab Sci 36:365-406, 1999Google Scholar
  9. 9.
    Stehouwer CD, Jacobs C: Abnormalities of vascular function in hyperhomocystein-aemia: relationship to atherothrombotic disease. Eur J Pediatr 157:107-111, 1998Google Scholar
  10. 10.
    Brattström L, Lindgren A, Israelsson B, Andersson A, Hultberg B: Homocysteine and cysteine: determinants of plasma levels in middle-aged and elderly subjects. J Intern Med 236:633-641, 1994Google Scholar
  11. 11.
    Koutroubakis IE, Dilaveraki E, Vlachonikolis IG, Vardas E, Vrentzos G, Ganotakis E, Mouzas IA, Gravanis A, Emmanouel D, Kouroumalis EA: Hyperhomocysteinemia in Greek patients with inflammatory bowel disease. Dig Dis Sci 45:2347-2351, 2000Google Scholar
  12. 12.
    Chowers Y, Sela BA, Holland R, Fidder H, Simoni FB, Bar-Meir S: Increased levels of homocysteine in patients with Crohn's disease are related to folate levels. Am J Gastroenterol 95:3498-3452, 2000Google Scholar
  13. 13.
    Oldenburg B, Fijnheer R, van de Griend R, van Berge-Henegouwen GP, Koningsberger JC: Homocysteine in inflammatory bowel disease: a risk factor for thromboembolic complications. Am J Gastroenterol 95:2825-2830, 2000Google Scholar
  14. 14.
    Coll P, Guttormsen AB, Berstad A: Gastrointestinal disease with elevated plasma homocysteine level. Tidsskr Nor Laegeforen 119:3577-3579, 1999Google Scholar
  15. 15.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265-275, 1951.Google Scholar
  16. 16.
    Fortin LJ, Genest J: Measurement of homocysteine in the prediction of arteriosklerosis. Clin Biochem 28:155-162, 1995Google Scholar
  17. 17.
    Aukrust P, Berge PK, Müller F, Ueland PM, Svardal AM, Fröland SS: Elevated plasma levels of reduced homocysteine in common variable immunodeficiency—a marker of enhanced oxidative stress. Eur J Clin Invest 27:723-730, 1997Google Scholar
  18. 18.
    Moat SJ, Bonham JR, Powers HJ: Role of aminothiols as a component of the plasma antioxidant system and relevance to homocysteine-mediated vascular disease. Clin Sci 100:73-79, 2001Google Scholar
  19. 19.
    Hernanz A, Plaza A, Martin-Mola E, de Miguel E: Increased plasma levels of homocysteine and other thiol compounds in rheumatoid arthritis women. Clin Biochem 32:65-70, 1999Google Scholar
  20. 20.
    Fijnheer R, Roest M, Haas FJ, de Groot PG, Derksen RH: Homocysteine, methylenetetrahydrofolate reductase polymorphism, antiphospholipid antibodies, and thromboembolic events in systemic lupus erythematosus: a retrospective cohort study. J Rheumatol 25:1737-1742, 1998Google Scholar
  21. 21.
    Ueland PM, Mansoor MA, Guttormsen AB, Muller F, Aukrust P, Refsum H, Svardal AM: Reduced, oxidized and protein-bound forms of homocysteine and other aminothiols in plasma comprise the redox thiol status-a possible element of the extracellular antioxidant defense system. J Nutr 126:1281-1284, 1996Google Scholar
  22. 22.
    Mills BJ, Weiss MM, Lang CA, Liu MC, Ziegler C: Blood glutathione and cysteine changes in cardiovascular disease. J Lab Clin Med 135:396-401, 2000Google Scholar
  23. 23.
    Slot WB, van Kasteel V, Coerkamp EG, Seelen PJ, van der Werf SDJ: Severe thrombotic complications in a postpartum patient with active Crohn's disease resulting in ischemic spinal cord injury. Dig Dis Sci 40:1395-1399, 1995Google Scholar
  24. 24.
    Podolsky DK, Isselbacher KJ. Glycoprotein composition of colonic mucosa. Specific alterations in ulcerative colitis. Gastroenterology 87:991-998, 1984Google Scholar
  25. 25.
    Mahmud N, Molloy A, McPartlin J, Corbally R, Whitehead AS, Scott JM, Weir D: Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and ist clinical implications. Gut 45:389-394, 1999Google Scholar
  26. 26.
    Portela E, Lerias C, Palmeiro A, Ferrer-Antunes C, Leitao M, Freitas D: Homocysteine and MTHFR C677 mutation in inflammatory bowel disease. Gut 45(suppl):A15, 1999Google Scholar
  27. 27.
    øvrebö KK, Svardal A: The effect of glutathione modulation on the concentration of homocysteine in plasma of rats. Pharmacol Toxicol 87:103-107, 2000Google Scholar
  28. 28.
    Corona G, Toffoli G, Fabris M, Viel A, Zarrelli A, Donada C, Boiocchi M: Homocysteine accumulation in human ovarian carcinoma ascitic/cystic fluids possibly caused by metabolic alteration of the methionine cycle in ovarian carcinoma cells. Eur J Cancer 33:1284-1290, 1997Google Scholar
  29. 29.
    Lambert D, Benhayoun S, Adjalla C, Gelot M, Renkes P, Felden F, Gerard P, Belleville F, Gaucher P, Gueant JL, Nicolas JP: Crohn's disease and vitamin B12 metabolism. Dig Dis Sci 41:1417-1422, 1996Google Scholar
  30. 30.
    Lucock MD, Daskalakis IG, Wild J, Anderson A, Schorah CJ, Lean MEJ: The influence of dietary folate and methionine on the metabolic disposition of endotoxic homocysteine. Biochem Mol Med 59:104-111, 1996Google Scholar
  31. 31.
    Parnetti L, Bottiglieri T, Lowenthal D: Role of homocysteine in age-related vascular and non-vascular diseases. Aging Clin Exp Res 9:241-257, 1997Google Scholar
  32. 32.
    Langman LJ, Cole DEC: Homocysteine: Cholesterol of the 90s? Clin Chim Acta 286:63-80, 1999Google Scholar
  33. 33.
    Kim Y, Fawaz K, Knox T, Lee YM, Norton R, Arora S, Paiva L, Mason JB: Colonic mucosal concentrations of folate correlate well with blood measurements of folate staus in persons with colorectal polyps. Am J Clin Nutr 68:866-872, 1998Google Scholar
  34. 34.
    Brattström LE, Hultberg BL, Hardebo JE: Folic acid responsive postmenopausal homocysteinemia. Metabolism 11:1073-1077, 1985Google Scholar
  35. 35.
    Cattaneo M, Vecchi M, Zighetti ML, Saibeni S, Martinelli I, Omodei P, Mannucci PM, de Franchis R: High prevalence of hyperhomocysteinemia in patients with inflammatory bowel disease: a pathogenetic link with thromboembolic complications? Thromb Haemost 80:542-545, 1998Google Scholar
  36. 36.
    Franken DG, Boers GH, Blom HJ, Trijbels FJ, Kloppenborg PW: Treatment of mild hyperhomocysteinemia in vascular disease patients. Arterioscler Thromb 14:465-470, 1994Google Scholar
  37. 37.
    Hernanz A, Fernandez-Vivancos E, Montiel C, Vasquez JJ, Arnalich F: Changes in the intracellular homocysteine and glutathione content associated with aging. Life Sci 67:1317-1324, 2000Google Scholar
  38. 38.
    Nygard O, Vollset SE, Refsum H, Stensvold I, Tverdal A, Nordrehau JE, Ueland M, Kvale G: Total plasma homocysteine and caediovascular risk profile. JAMA 274:1526-1533, 1995Google Scholar
  39. 39.
    Boers GH, Smals AG, Trijbels FJ, Leermakers AI, Kloppenborg PW: Unique efficiency of methionine metabolism in in premanopausal women may protect against vascular disease in the reproductive years. J Clin Invest 72:1971-1976, 1983Google Scholar
  40. 40.
    Andersson A, Brattstrom L, Israelsson B, Isaksson A, Hamfelt A, Hultberg B: Plasma homocysteine before and after methionine loading with regard to age, gender, and menopausal status. Eur J Clin Invest 22:79-87, 1992Google Scholar
  41. 41.
    Krogh-Jensen M, Ekelund S, Svendsen L: Folate and homocysteine status and haemolysis in patients treated with sulphasalazine for arthritis. Scand J Clin Lab Invest 56:421-429, 1996Google Scholar
  42. 42.
    Morgenstern I, Hoensch H, Peters WHM, Roelofs HMJ, Kirch W: Influence of clinical factors, diet and drugs on the human upper gastrointestinal glutathione system. Gut (in press)Google Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • I. Morgenstern
    • 1
    Email author
  • M.T.M. Raijmakers
    • 2
  • W.H.M. Peters
    • 2
  • H. Hoensch
    • 3
  • W. Kirch
    • 4
  1. 1.The Institute of Clinical Pharmacology, Medical FacultyTechnical University DresdenDresdenGermany
  2. 2.Department of GastroenterologyUniversity Hospital St. RadboudNijmegenThe Netherlands
  3. 3.Department of GastroenterologyGeneral Hospital of Gross-GerauGross-GerauGermany
  4. 4.The Institute of Clinical Pharmacology, Medical FacultyTechnical University DresdenDresdenGermany

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