转甲基
蛋氨酸
同型半胱氨酸
蛋氨酸合酶
化学
内科学
生物化学
内分泌学
脂肪性肝炎
亚甲基四氢叶酸还原酶
甲硫醇
新陈代谢
半胱氨酸
生物
脂肪肝
氨基酸
医学
酶
基因型
有机化学
基因
硫黄
疾病
作者
Satish C. Kalhan,John M. Edmison,Susan Marczewski,Srinivasan Dasarathy,Lourdes L. Gruca,Carole Bennett,Clarita Duenas,Rocío López
出处
期刊:Clinical Science
[Portland Press]
日期:2011-05-04
卷期号:121 (4): 179-189
被引量:65
摘要
Hepatic metabolism of methionine is the source of cysteine, the precursor of glutathione, the major intracellular antioxidant in the body. Methionine also is the immediate precursor of SAM (S-adenosylmethionine) the key methyl donor for phosphatidylcholine synthesis required for the export of VLDL (very-low-density lipoprotein) triacylglycerols (triglycerides) from the liver. We have examined the kinetics of methionine, its transmethylation and trans-sulfuration with estimates of whole body rate of protein turnover and urea synthesis in clinically stable biopsy-confirmed subjects with NASH (non-alcoholic steatohepatitis). Subjects with NASH were more insulin-resistant and had significantly higher plasma concentrations of usCRP (ultrasensitive C-reactive protein), TNFα (tumour necrosis factor α) and other inflammatory cytokines. There was no significant effect of insulin resistance and NASH on whole body rate of protein turnover [phenylalanine Ra (rate of appearance)] and on the rate of urea synthesis. The rates of methylation of homocysteine and transmethylation of methionine were significantly lower in NASH compared with controls. There was no difference in the rate of trans-sulfuration of methionine between the two groups. Enteric mixed nutrient load resulted in a significant increase in all the measured parameters of methionine kinetics. Heterozygosity for MTHFR (5,10-methylene-tetrahydrofolate reductase) (677C→T) did not have an impact on methionine metabolism. We speculate that, as a result of oxidant stress possibly due to high fatty acid oxidation, the activity of methionine adenosyltransferase is attenuated resulting in a lower rate of transmethylation of methionine and of SAM synthesis. These results are the first evidence for perturbed metabolism of methionine in NASH in humans and provide a rationale for the development of targeted intervention strategies.
科研通智能强力驱动
Strongly Powered by AbleSci AI