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)

Homocysteine interacts in a complex way in the plasma with cysteine and plasma proteins. To explore the interrelations between free and protein-bound homocysteine and cysteine during short- and long-term changes in plasma levels, free and bound homocysteine and cysteine were measured in 13 patients with homocystinuria due to cystathionine beta-synthase deficiency. Levels were measured during oral methionine loads (4 g/m2 body surface area) and after oral betaine (3 g twice daily). In six pyridoxine-responsive patients, free and bound levels of homocysteine and cysteine, measured 4 to 24 hours after oral methionine, changed in a parallel manner. Similar close tracking occurred in fasting plasma samples collected from two pyridoxine-nonresponsive patients before and during betaine therapy. Oral betaine given to seven pyridoxine-nonresponsive patients decreased free and bound homocysteine and increased free and bound cysteine toward normal levels during monitoring periods of up to 300 days. In these studies as the level of homocysteine decreased, the proportion of protein-bound homocysteine and cysteine increased. The present study establishes that changes in bound and free levels of either homocysteine or cysteine track closely in the short-term (four hours or less) and generally also in the long-term (up to 300 days).
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PMID:Free and protein-bound homocysteine and cysteine in cystathionine beta-synthase deficiency: interrelations during short- and long-term changes in plasma concentrations. 276 10

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

The cys2-1 mutation of Saccharomyces cerevisiae was originally thought to confer cysteine dependence through a serine O-acetyltransferase deficiency. In this study, we show that cys2-1 strains lack not only serine O-acetyltransferase but also cystathionine beta-synthase. However, a prototrophic strain was found to be serine O-acetyltransferase deficient because of a mutation allelic to cys2-1. Moreover, revertants obtained from cys2-1 strains had serine O-acetyltransferase but not cystathionine beta-synthase, whereas transformants obtained by treating a cys2-1 strain with an S. cerevisiae genomic library had cystathionine beta-synthase but not serine O-acetyltransferase. From these observations, we conclude that cys2-1 (serine O-acetyltransferase deficiency) accompanies a very closely linked mutation that causes cystathionine beta-synthase deficiency and that these mutations together confer cysteine dependence. This newly identified mutation is named cys4-1. These results not only support our previous hypothesis that S. cerevisiae has two functional cysteine biosynthetic pathways but also reveal an interesting gene arrangement of the cysteine biosynthetic system.
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PMID:Cysteine biosynthesis in Saccharomyces cerevisiae: mutation that confers cystathionine beta-synthase deficiency. 305 21

Homocystinuria due to cystathionine beta-synthase deficiency may be responsive to pyridoxine, a precursor of the cofactor pyridoxal phosphate, and the amount of residual enzyme activity present is the probable determinant of this. In six treated pyridoxine-responsive patients whose biochemical control of fasting plasma amino acid levels appeared optimal, we assessed the effects on plasma amino acids of standard oral methionine loads (4g/m2 of body area) before and after adding betaine (trimethylglycine) 6 g/d, to the treatment regimen of pyridoxine and folic acid. Our aim was to define the capacity of these patients to metabolize methionine and to determine whether betaine would effect a reduction in postload homocysteine levels. During the 24 hours after the methionine challenge all patients had higher plasma methionine and homocysteine and lower cysteine than did 17 normal subjects. After betaine these homocysteine responses were reduced to near normal, and there was a trend toward increased methionine. There was a direct correlation between premethionine fasting homocysteine and mean homocysteine responses during the 24 hours following the methionine load, both before (r = 0.79) and after betaine (r = 0.71). Betaine also increased plasma cysteine levels in patients with the more severe biochemical abnormalities. After betaine there were modest increases in plasma serine (mean increase 25%; P less than 0.025). Since the vascular complications of homocystinuria are related to increased plasma homocysteine, betaine therapy may reduce this risk in patients receiving a standard pyridoxine and folic acid regimen in whom there are abnormal homocysteine responses after a standard methionine load.
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PMID:Homocystinuria due to cystathionine beta-synthase deficiency--the effects of betaine treatment in pyridoxine-responsive patients. 393 99

Cell-free extracts of Bacillus megaterium form beta-cyanoalanine (beta-CNA)-(14)C from Na(14)CN and l-cysteine, O-acetyl-l-serine or, to a lesser extent, l-serine. However, the presence of cyanide in the growth medium does not increase the capacity of cell extracts to catalyze the formation of beta-CNA from cysteine and cyanide. The formation of beta-CNA is readily detected in extracts of cells grown in synthetic media with sulfate or l-djenkolic acid as sulfur sources; such cells also exhibit an increased ability to form cysteine when compared with cells grown on cysteine as the sulfur source. beta-CNA formation could not be detected in extracts of cells grown on cysteine as the sulfur source. A 40-fold purification of the O-acetyl-serine sulfhydrylase resulted in the co-purification of the beta-CNA-forming activity. The sulfhydrylase and the beta-CNA-forming activity co-chromatographed on diethyl-aminoethyl cellulose and Sephadex G-100.
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PMID:Formation of -cyanoalanine by O-acetylserine sulfhydrylase. 500 Nov 94

Control of coenzyme A (CoA) synthesis was studied in isolated perfused rat hearts. The data obtained support the hypothesis that phosphorylation of pantothenic acid by pantothenate kinase is the flux-generating reaction in the pathway of CoA synthesis. This reaction operated in the cell far removed from its thermodynamic equilibrium; it was saturated with substrates under all conditions studied; and the concentration of substrate changed in the opposite direction to flux when flux was altered. The reaction was subject to control by external factors associated with oxidation of glucose, pyruvate, or palmitate. CoA synthesis from 4'-phosphopantothenic acid was not inhibited by glucose and pyruvate, suggesting that pantothenate kinase is the only reaction in the pathway that is controlled in isolated hearts. Maximum rates of CoA synthesis in perfused hearts with pantothenate kinase stimulation were dependent on a supply of exogenous cysteine. Perfusate [14C]cysteine was incorporated into intermediates of this pathway and CoA. When protected from oxidation to cystine by low concentrations of dithiothreitol, 0.1 mM cysteine in the perfusate resulted in maximum rates of CoA synthesis. Evidence was obtained that indicates that addition of cysteine relieves a substrate limitation at the 4'-phosphopantothenyl cysteine synthase reaction.
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PMID:Pantothenate kinase and control of CoA synthesis in heart. 632 96

Mutants carrying defects in cysteine synthase A or B or both were isolated from Salmonella typhimurium LT2. Parent strains were able to grow on minimal media containing sulfate, sulfite, sulfide, or thiosulfate as sulfur sources. Mutants lacking cysteine synthase B were unable to grow on thiosulfate, whereas mutants lacking cysteine synthase A grew on the four inorganic sulfur sources described above with little difference in their growth rates. Mutants lacking both cysteine synthases failed to grow on media containing any of the inorganic sulfur sources tested. Purification of cysteine synthase B resulted in the copurification of S-sulfocysteine synthase. In addition, the two activities were also cotransduced. These activities appear to be associated with the cysM gene, and this is able to be cotransducted with the cysK gene at a high frequency. From these results, it may be concluded that thiosulfate is assimilated via S-sulfocysteine exclusively with the aid of S-sulfocysteine synthase.
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PMID:Evidence that thiosulfate assimilation by Salmonella typhimurium is catalyzed by cysteine synthase B. 635 63

S-Sulfocysteine synthase was isolated from Salmonella typhimurium LT-2 to homogeneous form with polyacrylamide gel electrophoresis. The molecular weight of this enzyme was determined to be ca. 55,000. The enzyme consisted of two identically sized subunits, and it contained one pyridoxal phosphate per subunit. The enzyme catalyzed the biosynthesis of cysteine or S-methylcysteine from sulfide or methanethiol and O-acetylserine, respectively, in addition to the formation of S-sulfocysteine from thiosulfate and O-acetylserine. The enzyme is identical to cysteine synthase B. The intracellular level of this enzyme was regulated by lesser extents of the same factors as those effective for cysteine synthase A.
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PMID:Enzymatic proof for the identity of the S-sulfocysteine synthase and cysteine synthase B of Salmonella typhimurium. 637 37

Several sul-reg mutants of Aspergillus nidulans isolated as constitutive for arylsulphatase were studied with respect to the regulation of enzymes involved in cysteine and homocysteine synthesis and to the pool of sulphur amino acids. All mutants examined showed a decreased concentration of glutathione as compared with the wild type, and all mutants, with one exception, had a decreased total pool of sulphur amino acids. The results suggest that the mutants are leaky in the sulphate assimilation pathway. They show derepression of cysteine synthase, homocysteine synthase, cystathionine beta-synthase and gamma-cystathionase. In spite of having derepressed homocysteine synthase, the enzyme which constitutes an alternative pathway for homocysteine synthesis, the sul-reg mutations do not suppress lesions in genes required for the main homocysteine-synthesizing pathway. This indicates that the derepression of homocysteine synthase is not in itself sufficient for physiological functioning of this enzyme, but seems to depend also on the effectiveness of cysteine synthesis and sulphide formation.
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PMID:Mutations affecting the sulphur assimilation pathway in Aspergillus nidulans: their effect on sulphur amino acid metabolism. 638 43

1. Regulation of four enzymes involved in cysteine and homocysteine synthesis, i.e. cysteine synthase (EC 4.2.99.8), homocysteine synthase (EC 4.1.99.10), cystathionine beta-synthase (EC 2.1.22) and gamma-cystathionase (EC 4.4.1.1) was studied in the wild type and sulphur regulatory mutants of Neurospora crassa. 2. Homocysteine synthase and cystathionine beta-synthase were found to be regulatory enzymes but only the former is under control of the cys-3 - scon system regulating several enzymes of sulphur metabolism, including gamma-cystathionase. 3. The results obtained with the mutants strongly suggest that homocysteine synthase plays a physiological role as an enzyme of the alternative pathway of methionine synthesis. Cysteine synthase activity was similar in all strains examined irrespective of growth conditions. 4. The sconc strain with derepressed enzymes of sulphur metabolism showed an increased pool of sulphur amino acids, except for methionine. Particularly characteristic for this pool is a high content of hypotaurine, a product of cysteine catabolism.
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PMID:Effect of regulatory mutations of sulphur metabolism on the levels of cysteine- and homocysteine-synthesizing enzymes in Neurospora crassa. 645 95


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