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

A modest homocysteine elevation is associated with an increased cardiovascular risk. Marked circulating homocysteine elevations occur in homocystinuria due to cystathionine beta-synthase (CbetaS) deficiency, a disorder associated with a greatly enhanced cardiovascular risk. Lowering homocysteine levels reduces this risk significantly. Because homocysteine-induced oxidative damage may contribute to vascular changes and extracellular superoxide dismutase (EC-SOD) is an important antioxidant in vascular tissue, we assessed EC-SOD and homocysteine in patients with homocystinuria. We measured circulating EC-SOD, total homocysteine (free plus bound), and methionine levels during the treatment of 21 patients with homocystinuria, 18 due to CbetaS deficiency, aged 8 to 59 years, and 3 with remethylating defects. We measured total homocysteine by immunoassay, EC-SOD by ELISA, and methionine by amino acid analysis and assessed interindividual and intraindividual relationships. There was a significant, positive relationship between EC-SOD and total homocysteine. For the interindividual assessment, levels were highly correlated, r=0.746, N=21, P<0.0001. This relationship was maintained after taking into account intraindividual patient variation (r=0.607, N=62, P<0.0001). In 2 newly diagnosed CbetaS-deficient patients, treatment that lowered the markedly elevated pretreatment homocysteine level (from 337 to 72 and from 298 to 50 micromol/L) reduced the associated elevated EC-SOD in each by 50%. EC-SOD and methionine levels were unrelated (r=0.148, n=39, P=0.368). The positive relationship between circulating EC-SOD and homocysteine could represent a protective antioxidant response to homocysteine-induced oxidative damage and contribute to reducing cardiovascular risk in homocystinuric patients. EC-SOD levels may be relevant to the pathogenesis of vascular disease in other patient groups.
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PMID:Relationship between homocysteine and superoxide dismutase in homocystinuria: possible relevance to cardiovascular risk. 1080 30