期刊
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
卷 8, 期 2, 页码 211-219出版社
TAYLOR & FRANCIS LTD
DOI: 10.1586/17512433.2015.1010516
关键词
atherosclerosis; homocysteine; lipoprotein; microorganisms; oxidative phosphorylation; oxidative stress; thioretinaco; thioretinamide
资金
- US Department of Veterans Affairs
The homocysteine theory of arteriosclerosis was discovered by study of arteriosclerotic plaques occurring in homocystinuria, a disease caused by deficiencies of cystathionine synthase, methionine synthase or methylenetetrahydrofolate reductase. According to the homocysteine theory, metabolic and nutritional abnormalities leading to elevation of plasma homocysteine cause atherosclerosis in the general population without these rare enzymatic abnormalities. Through studies of metabolism of homocysteine thiolactone, the anhydride of homocysteine, in cell cultures from homocystinuric children, the pathway for synthesis of sulfate was found to be dependent upon thioretinamide, the amide formed from retinoic acid and homocysteine thiolactone. Two molecules of thioretinamide form the complex thioretinaco with cobalamin, and oxidative phosphorylation is catalyzed by reduction of oxygen, which is bound to thioretinaco ozonide, by electrons from electron transport particles. Atherogenesis is attributed to formation of aggregates of homocysteinylated lipoproteins with microorganisms, which obstruct the vasa vasorum during formation of arterial vulnerable plaques.
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