Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.1.22 (cystathionine beta-synthase)
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An elevation in the concentration of total plasma homocysteine is known to be an independent risk factor for the development of vascular disease. Alterations in homocysteine metabolism have also been observed clinically in diabetic patients. Patients with either type 1 or type 2 diabetes who have signs of renal dysfunction tend to exhibit elevated total plasma homocysteine levels, whereas type 1 diabetic patients who have no clinical signs of renal dysfunction have lower than normal plasma homocysteine levels. The purpose of this study was to investigate homocysteine metabolism in a type 1 diabetic animal model and to examine whether insulin plays a role in its regulation. Diabetes was induced by intravenous administration of 100 mg/kg streptozotocin to Sprague-Dawley rats. We observed a 30% reduction in plasma homocysteine in the untreated diabetic rat. This decrease in homocysteine was prevented when diabetic rats received insulin. Transsulfuration and remethylation enzymes were measured in both the liver and the kidney. We observed an increase in the activities of the hepatic transsulfuration enzymes (cystathionine beta-synthase and cystathionine gamma-lyase) in the untreated diabetic rat. Insulin treatment normalized the activities of these enzymes. The renal activities of these enzymes were unchanged. These results suggest that insulin is involved in the regulation of plasma homocysteine concentrations by affecting the hepatic transsulfuration pathway, which is involved in the catabolism of homocysteine.
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PMID:Effects of streptozotocin-induced diabetes and of insulin treatment on homocysteine metabolism in the rat. 983 32

Research in the last two decades has transformed the way hydrogen sulphide (H2S) is perceived from a noxious gas to a gaso-transmitter with a vast potential in pharmacotherapy. H2S is synthesized in various body-systems using the enzymes cystathionine beta-synthase and cystathionine gamma-lyase; either of these being the predominat enzyme in a particular system. H2S may be one of the physiological modulators of blood pressure in humans. The gas relaxes the vascular smooth muscle cells by opening up K(ATP) channels. Moreover, it suppresses the proliferation of vascular smooth muscle cells. H2S may also be contributing in the protection afforded by ischaemia-preconditioning. Testosterone is thought to be responsible for the higher central nervous system level of H2S in males. In the central nervous system, H2S is implicated in Alzheimer's disease, epilepsy, stroke and Down's syndrome. Insulin secretion is associated with a decrease in the H2S levels. Raised H2S is detrimental in acute pancreatitis as well as in septic shock. Recently, H2S-releasing derivatives of certain drugs have shown promise in protection against gastric ulcer and in inflammatory bowel disease. The beneficial effects of certain sulphur containing herbs like ginseng and garlic may be mediated via H2S. In future, development of specific drugs modulating H2S levels may prove beneficial in varied disorders.
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PMID:Gaso-transmitter hydrogen sulphide: potential new target in pharmacotherapy. 2111 45