Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.1.22 (cystathionine beta-synthase)
 965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperhomocysteinemia has been suggested as a potent new risk factor for premature cardiovascular disease. Homocsyteine can induce endothelial cell injury but the mechanism is not understood. The purpose of this study was to evaluate the role of free radicals as potential causes of endothelial cell injury in a case-control study of obligate heterozygotes for cystathionine beta-synthase deficiency. Firstly, free radical production as measured by neutrophil chemiluminescence in obligate heterozygotes for cystathionine beta-synthase deficiency was compared with age- and sex-matched normal subjects. Secondly, the response of the cellular antioxidant system was examined by measuring the enzymes superoxide dismutase and glutathione peroxidase, their cofactors (selenium, copper), vitamin E and vitamin A in heterozygotes and normal subjects. Analyses of neutrophil chemiluminescence, vitamin A and E, glutathione peroxidase, selenium and copper showed no difference between heterozygotes and controls. While superoxide dismutase activity was higher in heterozygotes than normal subjects, the difference did not reach statistical significance and the hypothesis of excess free radical production as a mechanism of injury was not confirmed. However, further examination of superoxide dismutase activity in a larger number of subjects would be of interest.
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PMID:The role of free radicals as mediators of endothelial cell injury in hyperhomocysteinemia. 142 78

In certain tissues, glutathione biosynthesis is connected to methionine metabolism via the trans-sulfuration pathway. The latter condenses homocysteine and serine to cystathionine in a reaction catalyzed by cystathionine beta-synthase followed by cleavage of cystathionine to cysteine and alpha-ketoglutarate by gamma-cystathionase. Cysteine is the limiting amino acid in glutathione biosynthesis, and studies in our laboratory have shown that approximately 50% of the cysteine in glutathione is derived from homocysteine in human liver cells. In this study, we have examined the effect of pro- and antioxidants on the flux of homocysteine through the trans-sulfuration pathway in the human hepatoma cell line, HepG2. Our studies reveal that pyrrolidine dithiocarbamate and butylated hydroxyanisole enhance the flux of homocysteine through the trans-sulfuration pathway as has been observed previously with the pro-oxidants, H(2)O(2) and tertiary butyl hydroperoxide. In contrast, antioxidants such as catalase, superoxide dismutase and a water-soluble derivative of vitamin E elicit the opposite effect and result in diminished flux of homocysteine through the trans-sulfuration pathway. These studies provide the first evidence for the reciprocal sensitivity of the trans-sulfuration pathway to pro- and antioxidants, and demonstrate that the upstream half of the glutathione biosynthetic pathway (i.e. leading to cysteine biosynthesis) is redox sensitive as is the regulation of the well-studied enzymes in the downstream half (leading from cysteine to glutathione), namely, gamma-glutamyl-cysteine ligase and glutathione synthetase.
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PMID:Redox regulation of homocysteine-dependent glutathione synthesis. 1263 46