Homocysteine metabolism and the oxidative modification of proteins and lipids.
Altered homocysteine metabolism is implicated as a pathogenic factor in atherogenesis, neoplasia, and aging. Hereditary enzymatic deficiencies and nutritional deficiencies of folate, pyridoxine, or cobalamin are associated with elevated blood homocysteine, accelerated atherosclerosis, and manifestations of aging. The failure of malignant cells to metabolize homocysteine thiolactone to sulfate is attributed to deficiency of thioretinaco, a complex containing cobalamin, homocysteine thiolactone, and retinoic acid. The sulfhydryl group of homocysteine is believed to act catalytically with ferric or cupric ions in a mixed function oxidation system to generate hydrogen peroxide, oxygen radicals, and homocysteinyl radicals. These reactive species may interact with the active site of enzyme protein to cause inactivation of catalytic activity. Homocysteine thiolactone is oxidized to sulfate by a process involving ascorbate, thioretinamide, and superoxide, under the control of thyroxine and growth hormone. Thioretinaco is believed to be the active site of adenosine triphosphate (ATP) binding in oxidative phosphorylation with the participation of oxygen, ascorbate, proton gradient, and electron transport. Depletion of thioretinaco from mitochondrial and microsomal membranes may be associated with increased formation and release of radical oxygen species within neoplastic and senescent cells. Specific proposals are made for investigating the importance of homocysteine metabolism in the oxidative modification of proteins and lipids.
Olszewski
A J
AJ
Department of Physiology and Biochemistry of Nutrition, National Food and Nutrition Institute, Warsaw, Poland.
McCully
K S
KS
D000375:Aging / Q000378:metabolism; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D005609:Free Radicals / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D005609:Free Radicals; D011506:Proteins; D013438:Sulfhydryl Compounds; D006710:Homocysteine