Inflammation causes tissue specific alterations of methionine synthase

• Main Authors: Wei-Wen Chen, 陳韋文
• Other Authors: 蔣恩沛
• Format: Others
• Language: en_US
• Online Access: http://ndltd.ncl.edu.tw/handle/92738403958753752079

碩士 === 國立中興大學 === 食品暨應用生物科技學系所 === 97 === Background. The impact of inflammation on specific enzymes involved in the one-carbon metabolism is unclear. Objective of the study was to investigate the impact of chronic inflammation on 5-methyltetrahydrofolate-homocysteine methyltransferase in vivo. Design and Methods. The expression of 5-methyltetrahydrofolate-homocysteine methyltransferase in patients with chronic inflammation and in healthy controls were compared. The TNF-α transgenic mouse carries a 3’-modified human Tumor Necrosis Factor (TNF) transgene that exhibits upregulated TNF expression and progressive development of severe inflammation was used to study the impacts of chronic inflammation on 5-methyltetrahydrofolate-homocysteine methyltransferase in vivo. Methionine transmethylation metabolites were compared between the TNF-α transgenic and wild type mice. The activity and the protein quantity of 5-methyltetrahydrofolate-homocysteine methyltransferase were determined by radioisotope enzymatic assay and western blot. The effect of TNF overexpression on homocysteine remethylation and transsulfuration metabolic fluxes were investigated using stable isotopic tracers and Gas Chromatography/Mass Spectrometry. Results. TNF overexpression decreased 5-methyltetrahydrofolate-homocysteine methyltransferase protein in a tissue specific manner in our mouse model. Data from the labeling experiments suggested that folate-dependent homocysteine remethylation were reduced in transgenic mice compared to that of the wild type mice. Hepatic homocysteine transsulfuration flux of TNF-α transgenic mice appeared to be induced compared to the wild-type mice only in the female mice. De novo purine and pyrimidine synthesis were significantly reduced in specific tissues. Conclusion Inflammation altered 5-methyltetrahydrofolate-homocysteine methyltransferase in a tissue and gender specific manner.