Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Sulfur metabolism in gram-positive bacteria is poorly characterized. Information on the molecular mechanisms of regulation of genes involved in sulfur metabolism is limited, and no regulator genes have been identified. Here we describe the regulation of the lactococcal metC-cysK operon, encoding a cystathionine beta-lyase (metC) and cysteine synthase (cysK). Its expression was shown to be negatively affected by high concentrations of cysteine, methionine, and glutathione in the culture medium, while sulfur limitation resulted in a high level of expression. Other sulfur sources tested showed no significant effect on metC-cysK gene expression. In addition we found that O-acetyl-l-serine, the substrate of cysteine synthase, was an inducer of the metC-cysK operon. Using a random mutagenesis approach, we identified two genes, cmbR and cmbT, involved in regulation of metC-cysK expression. The cmbT gene is predicted to encode a transport protein, but its precise role in regulation remains unclear. Disruption of cmbT resulted in a two- to threefold reduction of metC-cysK transcription. A 5.7-kb region containing the cmbR gene was cloned and sequenced. The encoded CmbR protein is homologous to the LysR family of regulator proteins and is an activator of the metC-cysK operon. In analogy to CysB from Escherichia coli, we propose that CmbR requires acetylserine to be able to bind the activation sites and subsequently activate transcription of the metC-cysK operon.
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PMID:Regulation of the metC-cysK operon, involved in sulfur metabolism in Lactococcus lactis. 1174 47

Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous gas, it is endogenously produced in the brain. Physiological concentrations of H2S selectively enhance NMDA receptor-mediated responses and alter the induction of hippocampal long-term potentiation (LTP). Here we use cystathionine beta-synthase (CBS) knock-out mice to clearly show that CBS produces endogenous H2S in the brain and that H2S production is greatly enhanced by the excitatory neurotransmitter l-glutamate, as well as by electrical stimulation. This increased CBS activity is regulated by a pathway involving Ca2+/calmodulin. In addition, LTP is altered in CBS knock-out mice. These observations suggest that H2S is produced by CBS in response to neuronal excitation and that it may regulate some aspects of synaptic activity.
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PMID:Hydrogen sulfide is produced in response to neuronal excitation. 1520 38

Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous gas, it is endogenously produced in the brain from cysteine by cystathionine beta-synthase (CBS). H2S functions as a neuromodulator as well as a smooth muscle relaxant. Here we show that the levels of H2S are severely decreased in the brains of Alzheimer's disease (AD) patients compared with the brains of the age matched normal individuals. In addition to H2S production CBS also catalyzes another metabolic pathway in which cystathionine is produced from the substrate homocysteine. Previous findings, which showed that S-adenosyl-l-methionine (SAM), a CBS activator, is much reduced in AD brain and that homocysteine accumulates in the serum of AD patients, were confirmed. These observations suggest that CBS activity is reduced in AD brains and the decrease in H2S may be involved in some aspects of the cognitive decline in AD.
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PMID:Brain hydrogen sulfide is severely decreased in Alzheimer's disease. 1205 83

At least some mammalian tissues produce H2S in vitro from L-cysteine at rates sufficient to have physiological effects. To determine whether tissues of macrofaunal invertebrates have the same capacity, we measured H2S production in tissue homogenates of the Manila clam Tapes philippinarum and the lugworm Arenicola marina. Tissue homogenates from both animals produced significant quantities of H2S gas upon addition of L-cysteine and the enzyme cofactor pyridoxal-5PRIME;-phosphate (10 mmol l(-1) and 2 mmol l(-1), respectively), while only tissues from T. philippinarum produced measurable H2S in the absence of added substrate or cofactor. In T. philippinarum tissues, H2S production was completely inhibited by the cystathionine beta-synthase (CBS) inhibitor aminooxyacetic acid (AOAA), suggesting that the majority of H2S production was via CBS pathways, while in A. marina body wall, AOAA inhibited only half of the total H2S production, indicating that the CBS pathway was not the only major source of H2S production. H2S production in tissues of T. philippinarum but not A. marina was doubled by the addition of a second thiol substrate (2.5 mmol l(-1) 2-mercaptoethanol), suggesting the presence of an 'activated serine sulfhydrase pathway', which had previously been demonstrated only in some microfauna.
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PMID:Enzymatic hydrogen sulfide production in marine invertebrate tissues. 1216 Aug 76

H2S is produced from cysteine by cystathionine beta-synthase (CBS) in the brain and functions as a neuromodulator. Although the production of H2S is regulated by Ca2+ and calmodulin in response to neuronal excitation, little is known about the molecular mechanism for the regulation in CBS activity. Here we show that four cysteine residues of CBS are involved in the regulation of its activity in the presence of Ca2+ and calmodulin. Sodium nitroprusside (SNP), a modifying agent for cysteine residues, enhances CBS activity, whereas N-ethylmaleimide, an alkylating agent for cysteine residues, completely abolished the effect of SNP. Site-directed mutagenesis of the 13 cysteine residues of CBS identified four cysteine residues that are involved in the regulation of CBS activity by SNP, and two of the four residues are involved in the regulation of the basal CBS activity. The enhancement of CBS activity by SNP is independent of nitric oxide production. In the presence of Staphylococcus aureus alpha-hemolysin, which permeabilizes the cell membrane, exogenously applied SNP enhances the activity of CBS in intact cells. The present study demonstrates a novel mechanism for the regulation of CBS activity and provides a possible therapeutic application of SNP for the diseases in which CBS activity is deficient.
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PMID:A novel enhancing mechanism for hydrogen sulfide-producing activity of cystathionine beta-synthase. 1221 17

Hydrogen sulfide (H2S) is endogenously produced in the brain from L-cysteine by the enzyme cystathionine beta-synthase (CBS) and functions as a neuromodulator in the brain. H2S selectively enhances NMDA receptor-mediated responses and alters hippocampal long-term potentiation (LTP). The production of H2S is regulated by Ca2+/calmodulin-mediated pathways and is enhanced in response to neuronal excitation. In addition to this fast regulation, we describe here a slower form of the regulation of H2S production by testosterone and S-adenosyl-L-methionine (SAM), a CBS activator. Endogenous H2S in the mouse brain increases after birth, reaches a maximum level at 8 weeks and then decreases. Female brain contains less H2S than male brain at each age. A single administration of testosterone to female mice increases the endogenous H2S and SAM, which reach levels similar to those of male mice. In contrast, castration of male mice decreases the levels of testosterone, SAM and H2S in the brain. Administration of SAM once a day for 3 days increases the brain H2S without significantly changing the testosterone level. These observations suggest that testosterone can regulate the brain H2S level via changing the level of SAM.
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PMID:The production of hydrogen sulfide is regulated by testosterone and S-adenosyl-L-methionine in mouse brain. 1593 80

Hydrogen sulfide (H2S) is a well-known toxic gas with the smell of rotten eggs. Since the first description of the toxicity of H2S in 1713, most studies about H2S have been devoted to its toxic effects. Recently, H2S has been proposed as a physiologically active messenger. Three groups discovered that the brain contains relatively high concentrations of endogenous H2S. This discovery accelerated the identification of an H2S-producing enzyme, cystathionine beta-synthase (CBS) in the brain. In addition to the well-known regulators for CBS, S-adenosyl-L-methionine (SAM) and pyridoxal-5'-phosphate, it was recently found that Ca2+/calmodulin-mediated pathways are involved in the regulation of CBS activity. H2S is produced in response to neuronal excitation, and alters hippocampal long-term potentiation (LTP), a synaptic model for memory. can also regulate the release of corticotropin-releasing hormone (CRH) from hypothalamus. Another H2S producing enzyme, cystathionine gamma-lyase (CSE), has been identified in smooth muscle, and H2S relaxes smooth muscle in synergy with nitric oxide (NO). Recent progress in the study of H2S as a novel neuromodulator/transmitter in the brain is briefly reviewed.
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PMID:Hydrogen sulfide as a neuromodulator. 1239 53

Tissue concentrations of both homocysteine (Hcy) and cysteine (Cys) are maintained at low levels by regulated production and efficient removal of these thiols. The regulation of the metabolism of methionine and Cys is discussed from the standpoint of maintaining low levels of Hcy and Cys while, at the same time, ensuring an adequate supply of these thiols for their essential functions. S-Adenosylmethionine coordinately regulates the flux through remethylation and transsulfuration, and glycine N-methyltransferase regulates flux through transmethylation and hence the S-adenosylmethionine/S-adenosylhomocysteine ratio. Cystathionine beta-synthase activity is also regulated in response to the redox environment, and transcription of the gene is hormonally regulated in response to fuel supply (insulin, glucagon, and glucocorticoids). The H2S-producing capacity of cystathionine gamma-lyase may be regulated in response to nitric oxide. Cys is substrate for a variety of anabolic and catabolic enzymes. Its concentration is regulated primarily by hepatic Cys dioxygenase; the level of Cys dioxygenase is upregulated in a Cys-responsive manner via a decrease in the rate of polyubiquitination and, hence, degradation by the 26S proteasome.
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PMID:Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. 1518 31

Recent studies suggest that apart from nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H2S) is another inorganic gaseous mediator in the cardiovascular system. H2S is synthesized from L-cysteine by either cystathionine beta-synthase (CBS) or cystathionin gamma--lyase (CSE), both using pyridoxal 5'-phosphate (vitamin B6) as a cofactor. CBS is the main H2S-producing enzyme in the brain and CSE is involved in H2S formation in the cardiovascular system. H2S induces hypotension in vivo and vasodilation vitro by opening KATP channels in vascular smooth muscle cells. Chronic administration of CSE inhibitor induces arterial hypertension in the rat. In addition, decreased H2S generation has been demonstrated in the vasculature of spontaneously hypertensive rat, in experimental hypertension induced by NO synthase blockade, and in hypoxia-induced pulmonary hypertension, and administration of exogenous H2S donor has significant therapeutic effects in these models. Deficiency of H2S may contribute to atherogenesis in some patients with hyperhomocysteinemia, in whom the metabolism of homocysteine to cysteine and H2S is compromised by vitamin B6 deficiency. Reduced H2S production in the brain was observed in patients with Alzheimer's disease. On the other hand, excess of H2S may lead to mental retardation in patients with Down's syndrome and may be involved in the pathogenesis of hypotension associated with septic shock.
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PMID:[Hydrogen sulfide as a biologically active mediator in the cardiovascular system]. 1528 Jul 98

The enzymes of the transsulfuration pathway also have the capacity to catalyze the desulfhydration of cysteine. Recent studies demonstrate a role of the transsulfuration enzymes, cystathionine gamma-lyase and cystathionine beta-synthase, in catalyzing the desulfhydration of cysteine in brain and smooth muscle. The H2S produced from cysteine functions as a neuromodulator and smooth muscle relaxant. In glutamatergic neurons, the production of H2S by cystathionine beta-synthase enhances N-methyl-D-aspartate (NMDA) receptor-mediated currents. In smooth muscle cells, H2S produced by cystathionine gamma-lyase enhances the outward flux of potassium by opening potassium channels, leading to hyperpolarization of membrane potential and smooth muscle relaxation.
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PMID:New roles for cysteine and transsulfuration enzymes: production of H2S, a neuromodulator and smooth muscle relaxant. 1549 68


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