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)

Homocysteine is a branch-point metabolite, the biological fate of which is linked to vitamin B12, reduced folates and vitamin B6. Various inborn defects in homocysteine metabolism, among which cystathionine beta-synthase deficiency is most common, lead to the clinical condition homocystinuria. A central feature of this clinical state is premature arteriosclerosis. These patients benefit from agents serving as cofactors in homocysteine metabolism which both reduce the homocysteine levels in plasma and the incidence of vascular episodes. Experimental data point to homocysteine as an arteriosclerotic agent. Homocysteine in human plasma exists mainly as mixed disulfides with albumin (70 per cent) and cysteine. New methods determine total plasma homocysteine which includes all these species. Normal values for plasma homocysteine are lower in premenopausal women than in men and postmenopausal women. Impaired homocysteine metabolism seems to exist in 15-30 per cent of patients with premature cardiovascular disease. Moderate homocysteinemia is as a risk factor for cardiovascular disease, independent of conventional risk factors. Apart from homocystinuria, vitamin B12 deficiency causes the most extreme elevations of plasma homocysteine, and it has been established that plasma homocysteine is a more responsive parameter to impaired vitamin B12 function than serum cobalamin. Massive increase in plasma homocysteine level is also observed in folate deficiency, whereas renal failure, some malignant states and psoriasis cause a moderate homocysteinemia. High doses of folic acid reduce plasma homocysteine, and this innocuous mean should be considered as an intervention in patients with increased plasma level. Drugs like methotrexate, some anticonvulsants and 6-azauridine triacetate induce moderate elevation of plasma homocysteine, whereas a reduction is observed after penicillamine administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Plasma homocysteine, a risk factor for premature vascular disease. Plasma levels in healthy persons; during pathologic conditions and drug therapy]. 281 54

Over the last 30 years, a growing body of evidence has documented the role of hyperhomocysteinemia (HHcy) as an independent vascular risk factor. However, the mechanisms through which elevated circulating levels of homocysteine (Hcy) cause vascular injury and promote thrombosis remain elusive. Most findings have been achieved in in vitro studies employing exceedingly high concentrations of Hcy, whereas only a few studies have been carried out in vivo in humans. In homocystinuric patients, homozygotes for mutations of the gene coding for the cystathionine beta-synthase enzyme, abnormalities of coagulation variables reflecting a hypercoagulable state, have been reported. In vitro studies provide a biochemical background for such a state. In homocystinuric patients, an in vivo platelet activation has also been reported. The latter abnormality is not corrected by the bolus infusion of concentrations of hirudin, which determines a long-lasting impairment of the conversion of fibrinogen to fibrin by thrombin; in contrast, it appears at least in part lowered by the administration of the antioxidant drug probucol. During the autooxidation of Hcy in plasma, reactive oxygen species are generated. The latter initiate lipid peroxidation in cell membranes (potentially responsible for endothelial dysfunction) and in circulating lipoproteins. Oxidized low-density lipoproteins (LDL) may trigger platelet activation as well as some of the hemostatic abnormalities reported in such patients. Thus the oxidative stress induced by Hcy may be a key process in the pathogenesis of thrombosis in HHcy. Accumulation of adenosylhomocysteine in cells (a consequence of high circulating levels of homocysteine) inhibits methyltransferase enzymes, in turn preventing repair of aged or damaged cells. This mechanism has been recently documented in patients with renal failure and HHcy and provides an additional direction to be followed to understand the tendency to thrombosis in moderate HHcy.
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PMID:Homocysteine, coagulation, platelet function, and thrombosis. 1101 42