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Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/52049
標題: The effects of sulfasalazine on homocysteine metabolism
Sulfasalazine 對於同半胱胺酸代謝之影響
作者: Wu, Yi-Ting
吳伊婷
關鍵字: Sulfasalazine;硫-腺核苷甲硫胺酸;S-adenosylmethionine;Methionine adenosyltransferase;甲硫胺酸硫腺核苷轉移酶
出版社: 食品暨應用生物科技學系所
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Anal Biochem 1998 Nov 15;264(2):180-4. (20) Yang J, He Y, Du YX, Tang LL, Wang GJ, Fawcett JP. Pharmacokinetic properties of S-adenosylmethionine after oral and intravenous administration of its tosylate disulfate salt: a multiple-dose, open-label, parallel-group study in healthy Chinese volunteers. Clin Ther 2009 Feb;31(2):311-20. (21) Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988 Mar;31(3):315-24. (22) Miller JW, Nadeau MR, Smith J, Smith D, Selhub J. Folate-deficiency-induced homocysteinaemia in rats: disruption of S-adenosylmethionine''s co-ordinate regulation of homocysteine metabolism. Biochem J 1994 Mar 1;298 ( Pt 2):415-9. (23) Lagendijk J, Ubbink JB, Vermaak WJ. Quantification of erythrocyte S-adenosyl-L-methionine levels and its application in enzyme studies. J Chromatogr 1992 Apr 15;576(1):95-101. (24) O''Broin S, Kelleher B. Microbiological assay on microtitre plates of folate in serum and red cells. J Clin Pathol 1992 Apr;45(4):344-7. (25) Cooney CA, Wise CK, Poirier LA. An improved sample preparation method for the quantitative HPLC determination of 5-methylcytidine in animal tissue. J Chromatogr 1997. (26) Melnyk S, Pogribna M, Pogribny IP, Yi P, James SJ. Measurement of plasma and intracellular S-adenosylmethionine and S-adenosylhomocysteine utilizing coulometric electrochemical detection: alterations with plasma homocysteine and pyridoxal 5''-phosphate concentrations. Clin Chem 2000 Feb;46(2):265-72. (27) Struys EA, Jansen EE, de MK, Jakobs C. Determination of S-adenosylmethionine and S-adenosylhomocysteine in plasma and cerebrospinal fluid by stable-isotope dilution tandem mass spectrometry. Clin Chem 2000 Oct;46(10):1650-6. (28) Loehrer FM, Angst CP, Brunner FP, Haefeli WE, Fowler B. Evidence for disturbed S-adenosylmethionine : S-adenosylhomocysteine ratio in patients with end-stage renal failure: a cause for disturbed methylation reactions? Nephrol Dial Transplant 1998 Mar;13(3):656-61. (29) Herrmann W, Schorr H, Obeid R, Makowski J, Fowler B, Kuhlmann MK. Disturbed homocysteine and methionine cycle intermediates S-adenosylhomocysteine and S-adenosylmethionine are related to degree of renal insufficiency in type 2 diabetes. Clin Chem 2005 May;51(5):891-7. (30) Telolahy P, Morel G, Cluet JL, Yang HM, Thieffry N, de CJ. An attempt to explain interindividual variability in 24-h urinary excretion of inorganic arsenic metabolites by C57 BL/6J mice. Toxicology 1995 Nov 30;103(2):105-12. (31) Wise CK, Cooney CA, Ali SF, Poirier LA. Measuring S-adenosylmethionine in whole blood, red blood cells and cultured cells using a fast preparation method and high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 1997 Aug 15;696(1):145-52. (32) Yeo EJ, Wagner C. Tissue distribution of glycine N-methyltransferase, a major folate-binding protein of liver. Proc Natl Acad Sci U S A 1994 Jan 4;91(1):210-4. (33) Kerr SJ. Competing methyltransferase systems. J Biol Chem 1972 Jul 10;247(13):4248-52. (34) Masson C, Cheron F. Infarct in the territory of the medial branch of the PICA. J Neurol Neurosurg Psychiatry 1990 Dec;53(12):1104-5. (35) Hyland K, Smith I, Bottiglieri T, Perry J, Wendel U, Clayton PT, et al. Demyelination and decreased S-adenosylmethionine in 5,10-methylenetetrahydrofolate reductase deficiency. Neurology 1988 Mar;38(3):459-62. (36) Stankova J, Shang J, Rozen R. Antisense inhibition of methylenetetrahydrofolate reductase reduces cancer cell survival in vitro and tumor growth in vivo. Clin Cancer Res 2005 Mar 1;11(5):2047-52. (37) Caruso I, Pietrogrande V. Italian double-blind multicenter study comparing S-adenosylmethionine, naproxen, and placebo in the treatment of degenerative joint disease. Am J Med 1987 Nov 20;83(5A):66-71. 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摘要: 
中文摘要
背景: Sulfasalazine，其抗發炎的機制為促進局部發炎組織其嘌呤核苷酸 (adenosine) 的釋出，而此作用則會造成三磷酸腺苷 (adenosine triphosphate, ATP) 的減少。三磷酸腺苷為合成硫-腺核苷甲硫胺酸之 (S-adenosylmethionine, adoMet) 前驅物，我們推測其含量降低可能會導致硫-腺核苷甲硫胺酸之合成也減少以及造成後續DNA 的低度甲基化。
本篇研究的目的則是要去探討是否sulfasalazine會直接地影響不同組織中硫-腺核苷甲硫胺酸的含量以及DNA 整體甲基化的程度。
實驗設計與方法: 以橫斷式研究法調查了台灣台中榮民總醫院免疫風濕科共133位罹患類風濕性關節炎之受測者; 並同時進行了動物實驗，分析與轉甲基作用有關的生化數值。分析其血液中同半胱胺酸及其相關的代謝物如葉酸、硫-腺核苷甲硫胺酸、硫-腺核苷同半胱胺酸之濃度，並測量了不同組織中硫-腺核苷甲硫胺酸合成酶之酵素活性。
結果: 服用sulfasalazine的病人其全血中硫-腺核苷甲硫胺酸的濃度增高了778%，而且sulfasalazine之劑量或服藥期間長短皆與全血中的硫-腺核苷甲硫胺酸成正相關。動物實驗顯示，sulfasalazine 顯著地改變不同組織中硫-腺核苷甲硫胺酸之含量。同樣地，負責合成硫-腺核苷甲硫胺酸之酵素在小鼠的不同組織中也觀察到不同地結果。
結論: Sulfasalazine 對於不同組織中硫-腺核苷甲硫胺酸的含量與合成酵素皆有不同的影響。
URI: http://hdl.handle.net/11455/52049
Appears in Collections:食品暨應用生物科技學系

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