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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)

Transcription of the genes for sulfur assimilation and methionine biosynthesis in Saccharomyces cerevisiae is regulated by the size of the intracellular pool of an organic sulfur compound. The identity of this compound is not clear, but suggestions include S-adenosylmethionine (SAM) and cysteine. By studying the repression of selected sulfur assimilation (MET) genes, we found that the ability to form cysteine from homocysteine is crucial for methionine-mediated repression to take place. The transcription of MET14 and MET25 could not be repressed by methionine in strains in which either STR4 (which encodes cystathionine beta-synthase) or STR1 (cystathionine gamma-lyase) was disrupted, whereas the repression was independent of GSH1 (which encodes the enzyme responsible for the first step in glutathione biosynthesis from cysteine). In contrast, cysteine could repress the MET genes in all of these strains. Two genes that presumably encode cystathionine gamma-synthase and cystathionine beta-lyase were identified by genetic disruption (ORFs YJR130c and YGL184c), yielding yeast strains that cannot convert cysteine into homocysteine. Repression by cysteine was possible in either disruptant, suggesting a role in repression for cysteine alone. While some repression of MET genes could be accomplished by homocysteine in a strain that cannot form SAM from methionine, a low intracellular level of SAM seems to be necessary for full cysteine-mediated repression to take place.
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PMID:Cysteine is essential for transcriptional regulation of the sulfur assimilation genes in Saccharomyces cerevisiae. 1082 Nov 89

Hyperhomocysteinemia is a well established risk factor for cardiovascular disease, and multiple factors likely lead to abnormal regulation of plasma homocysteine in patients with diabetes. To examine a possible role for insulin and glucose in homocysteine metabolism, we examined the activity of two important enzymes of homocysteine metabolism in hepatocytes. In various tissues of six mice, methylene tetrahydrofolate reductase (MTHFR) activity was present in all tissues tested and the highest concentration (per gram) was in the brain. In contrast, cystathionine beta-synthase (CBS) activity appeared to be present only in the liver and to a small extent in the kidney. Using HEP G2 cells in culture, MTHFR activity was 3.3+/-0.8 nmol/h when the glucose concentration in the medium was 100 mg/dl and fell to 2.3+/-0.3 nmol/h when glucose was increased to 300 mg/dl. MTHFR activity was 3.4+/-0.3 nmol/h when cells were exposed to an insulin concentration of 5 mU/ml and fell to 2.8+/-0.3 nmol/h when insulin concentration was increased to 200 mU/ml (P<0.01). In contrast CBS activity increased from 0.017 to 0.13 U/ml by increasing the glucose concentration in the medium (P<0.01), but decreased from 0.04 to 0.02 (P<0.01) when the insulin concentration was increased from 5 to 200 mU/ml, respectively. We conclude that CBS and MTHFR have different tissue distributions, with CBS being present predominantly in liver and kidney, and MTHFR found in many tissues. In addition, both insulin and glucose affect the activity of the two enzymes when added to hepatocytes in vitro. If such effects occur in humans with hyperglycemia and hyperinsulinemia, then alterations in homocysteine metabolism may contribute to the accelerated macrovascular disease associated with insulin resistance or type 2 diabetes.
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PMID:The effect of glucose and insulin on the activity of methylene tetrahydrofolate reductase and cystathionine-beta-synthase: studies in hepatocytes. 1158 7

Cystathionine beta-synthase (CBS) is a key enzyme that catalyzes the rate-limiting step for homocysteine (Hcy) metabolism via the trans-sulfuration pathway and is also responsible for the production of H(2)S through the desulfhydration reaction. Our recent studies demonstrate that renal ischemia/reperfusion decreased the CBS activity leading to Hcy accumulation and H(2)S reduction in the kidney, which in turn contributed to kidney injury. Both Hcy and H(2)S play important roles in physiological and pathological processes. In this study we investigated the molecular mechanism by which CBS activity was regulated in the kidney. The left kidney of Sprague-Dawley rat was subjected to 45 min of ischemia followed by 6 h of reperfusion. Ischemia/reperfusion caused a significant decrease in CBS mRNA and protein levels in the kidney. As a consequence, there was a marked reduction in the CBS enzyme activity. Transfection of kidney proximal tubular cells with transcription factor (Sp1) small interfering RNA caused a marked reduction in CBS mRNA, indicating a pivotal role for Sp1 in regulating CBS expression in kidney cells. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay detected a lower Sp1 activity in kidneys subjected to ischemia/reperfusion as compared with that in a sham-operated group. ERK-mediated phosphorylation of Sp1 was responsible for a decreased transcriptional activity of Sp1 in the kidney upon ischemia/reperfusion. These results suggest that reduced kidney CBS gene expression during ischemia/reperfusion is mediated via a decrease in Sp1 transcriptional activity. Regulation of CBS-mediated Hcy and H(2)S homeostasis may offer a renal protective effect against ischemia/reperfusion injury.
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PMID:Ischemia/reperfusion reduces transcription factor Sp1-mediated cystathionine beta-synthase expression in the kidney. 2039 94