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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)

Four enzymes necessary for the metabolism of methionine by the trans-sulfuration pathway, methionine adenosyltransferase (EC 2.5.1.6), adenosylhomocysteinase (EC 3.3.1.1), cystathionine beta-synthase (EC 4.2.1.22) and cystathionine gamma-lyase (EC 4.4.1.1) were identified in Tetrahymean pyriformis. The ability of these cells to transfer 35S from E135S]methionine to form [35S] cysteine was also observed and taken as direct evidence for the functional existence of this pathway in Tetrahymena. An intermediate in the pathway and an active methyl donor, S-adenosylmethionine, was qualitatively identified in Tetrahymena and its concentration was found to be greater in late stationary phase cells than in early stationary phase cells.
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PMID:The transsulfuration pathway in Tetrahymena pyriformis. 1 63

1. Cystathionine beta-synthase activity isolated from fibroblast cultures obtained from the skin of a normal and a homocystinuric individual were both cross-reactive with normal human liver cystathionine beta-synthase antibody. 2. Isoelectric focusing revealed a substantial difference in the isoelectric points of the normal and abnormal fibroblast enzymes. 3. Treatment of purified samples of normal and abnormal fibroblast enzymes with sodium dodecylsulphate followed by polyacrylamide gel electrophoresis indicated that both normal and abnormal enzymes were composed of two sub-units of molecular weights 53000 and 70000. 4. A combination of urea and sodium dodecylsulphate treatment revealed that the respective 53000 molecular weight sub-units were different. 5. It has been concluded that the molecular defect in the case of pyridoxine non-responsive homocystinuria examined in the present investigation arises as a result of an alteration in the structural gene which codes for the lower molecular weight sub-unit of cystathionine beta-synthase.
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PMID:The molecular defect in a case of (cystathionine beta-synthase)-deficient homocystinuria. 40 47

We have compared in vivo pyridoxine responsiveness with in vitro cystathionine beta-synthase activity in extracts of confluent fibroblasts from 14 synthase-deficient patients. Enzyme activity was measured with and without addition of its cofactor, pyridoxal-5'-phosphate, using a radioisotopic assay which detects as little as 0.25% of control activity. Six of seven lines from responsive patients had measurable activity without the added cofactor (0.6-15% of mean control). Two of these lines showed a five- and sevenfold stimulation of cystathionine beta-synthase activity with added pyridoxal-5'-phosphate; in the other four, the cofactor addition increased activity only modestly, as in controls. Two of seven lines from nonresponsive patients had measurable activity (each 3% of mean control) which increased two- and fivefold with the added cofactor. Cystathionine beta-synthase activity was undetectable in one line from a responsive patient and in five lines from nonresponsive ones. To characterize control and mutant synthase further, dissociation constants for pyridoxal-5'-phosphate were estimated and thermostability (54 degrees C) was studied in two control and five mutant lines. In one mutant, both parameters were normal; in the others, the affinity for the cofactor was reduced 3-to 11-fold and thermostability was much impaired. We conclude that at least three general classes of cystathionine beta-synthase mutants exist: those with no residual activity; those with reduced activity and normal affinity for pyridoxal-5' phosphate; and those with reduced activity and a reduced affinity for the cofactor. Pyridoxine responsiveness in vivo cannot be correlated simply with the presence or absence of residual synthase activity in vitro or with stimulation of in vitro enzyme activity by cofactor.
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PMID:Homocystinuria. Evidence for three distinct classes of cystathionine beta-synthase mutants in cultured fibroblasts. 64 Nov 46

In three experiments, activity of hepatic enzymes associated with metabolism of methionine through the transulfuration pathway were studied with respect to possible effects of diet and methionine infusion per abomasum. In experiment 1 no differences in methionine adenosyltransferase (MAT) or cystathionine lambda-lyase (CGL) were detected between lucerne and wheaten straw diets, or between effects of fasting for 48 h and 96 h after feeding lucrene chaff as opposed to fasting after feeding wheaten straw. Fasting for 96 h resulted in a trend toward increasing CGL and MAT specific activities on both diets. In experiment 2 MAT was depressed significantly by infusion of methionine at 1.4 g/day and to a greater extent by infusion at 4.2 g/day, whilst CGL was not significantly affected. In experiment 3 MAT specific activity decreased significantly in response to both levels of methionine supplementation. Betaine-homocysteine methyltransferase activity was increased by methionine infusion. CGL decreased in all treatments but there was a larger decrease in those animals receiving methionine infusion. No significant changes were observed in relation to other enzymes examined which included cystathionine beta-synthase and threonine dehydratase. These observations are consistent with the hypothesis that in sheep the increase in methionine in blood plasma which occurs when methionine is absorbed in increased amounts may be due to reduced entry into the transulfuration pathway because of a repression of MAT activity.
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PMID:The effect of diet and of methionine loading on activity of enzymes in the transulfuration pathway in sheep. 67 17

Cystathionine beta-synthase has been purified from human liver more than 3000-fold by a series of steps including high speed centrifugation, ammonium sulfate fractionation, chromatography on hydroxylapatite and DEAE-cellulose, gel filtration, preparative polyacrylamide gel electrophoresis, and glycerol density gradient centrifugation. The enzyme obtained is homogeneous as judged by polyacrylamide gel electrophoresis in four different systems: native, isoelectric focusing, in sodium dodecyl sulfate, and in 8 M urea. The native enzyme has an estimated molecular weight of 94,000 and is composed of two apparently identical subunits of 48,000. The pure enzyme has a specific activity of 160 units/mg of protein and contains tightly bound cofactor, pyridoxal 5' -phosphate. It is possesses serine sulfhydrase as well as cystathionine synthase activity. It has a broad pH optimum from 8.4 to 9.0, apparent Km values for L-serine of 1.15 mM and for L-homocysteine of 0.59 mM, and a pI of 5.2 The enzyme is stable over a pH range from 6.5 to 8.0 in phosphate buffers and can be stored in 40% glycerol at -15 degrees C for at least 1 month.
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PMID:Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits. 68 63

Theoretic and experimental arguments are surveyed which justify the setting up, within the family of pyridoxal-P-dependent lyases, of a special subgroup that comprizes several enzymes catalyzing exclusively beta-replacement reactions of alpha-aminoacids with electronegative substituents in the beta-position. The authors and their associates have studied the physico-chemical and catalytic properties of four high purity enzymes belonging to this subgroup, namely: cysteine lyase (EC 4.1.1.10) from embryonic chicken yolk-sac, serine sulfhydrase from chicken liver and the closely analogous or synonymic cystathionine beta-synthase (EC 4.4.1.8) from rat liver, and beta-cyanoalanine synthase (EC 4.4.1.9) from lupine seedlings, in comparison with some pyridoxal-P-requiring lyases differing in reaction specificity, for example, gamma-specific, alphabeta-eliminating or plurifunctional lyases such as gamma-cystathionase (EC 4.4.1.1) of animal tissues. The results of these studies, relating to subtrate and cosubstrate specificities of the enzymes mentioned, their interactions with some selective inhibitors, catalysis of isotopic exchange of hydrogen atoms in substrates and substrate analogs, etc., indicate that lyases of the exclusively beta-replacing type substantially differ in reaction mechanism from other subgroups of this enzyme family. Thus, it appears highly improbable that transient formation of an alphabeta-unsaturated, coenzyme-substrate imine, considered as an obligatory step in the action of lyases in the alphabeta-eliminating and other subgroups, should occur in the sequences of reaction intermediates in the case of beta-replacing lyases. Suggested features of the presumable catalytic mechanism of these lyases are discussed, such as : fixed conformation of the aminoacid substrate in the ES complex (protein-bound pyridoxal-P aldimine), with beta-substituent in orientation cis (rather than trans) to the Halpha atom ; role of the binding of appropriate cosubstrates (nucleophilic replacing agent, Cs) inducing essential electronic and/or steric transitions in the catalytic site of the ternanry CsES complexes, etc.
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PMID:The pyridoxal-phosphate-dependent enzymes exclusively catalyzing reactions of beta-replacement. 78 60

1. Methionine adenosyltransferase (ATP:L-methionine-S-adenosyl transferase, EC 2.5.1.6), cystathionine beta-synthase F1L-serine hydro-lyase (adding homocysteine), EC 4.2.1.22] and cystathionine gamma-lyase [L-cystathionine cysteine-lyase (deaminating), EC 4.4.1.1] activities were found only in the cytosol fraction of rat liver cells. None was found in the mitochondrial or endoplasmic reticulum fractions as judged by the distribution of marker enzymes on a density gradient after centrifugation of the cytoplasmic fraction of a liver homogenate, or in a preparation of liver cell nuclei. 2. Polymorphs, lymphocytes (with admixed monocytes) and mixed bone marrow white cells contained no methionine adenosyl transferase, cystathionine beta-synthase or cystathionine gamma-lyase activities. 3. The possible bearing of these results on the problem of abnormal cystine storage in cystinosis is briefly discussed.
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PMID:Methionine adenosyltransferase, cystathionine beta-synthase and cystathionine gamma-lyase activity of rat liver subcellular particles, human blood cells and mixed white cells from rat bone marrow. 105 81

Homolanthionine, a higher homologue of cystathionine, was found to accumulate in the mutants of Aspergillus nidulan impaired in the synthesis of methionine from homocysteine. The additional introduction of mutation resulting in a block at cystathionine gamma-synthase but not at cystathionine beta-synthase abolishes accumulation of both homolanthionine and cystathionine. This suggests a possible participation of cystathionine gamma-synthase in homolanthionine synthesis.
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PMID:Homolanthionine in fungi: accumulation in the methionine-requiring mutants of Aspergillus nidulans. 110 92

Three circumstances prompted us to reexamine the relationship between abnormal cystathionine accumulation and possible homocystinuria resulting from this condition: (a) discovery of an infant girl with apparently alternating massive cystathioninuria and homocystinuria; (b) the presence of homocystinuria in some, but not all, previously reported cases of cystathioninuria probably due to gamma-cystathionine deficiency; and (c) the recent demonstration that mammalian cystathionine beta-synthase can cleave cystathionine to homocysteine. The following conclusions were reached: (a) Homocystine may arise as a result of bacterial contamination of a urine sample initially containing cystathionine, but not homocystine. (b) After a methionine load, a cystathioninuric patient may excrete readily detected amounts of homocystine. (c) However, homocystinuria is not a necessary concomitant of even massive cystathioninuria. These findings and some of their implications are briefly discussed.
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PMID:Cystathioninuria and homocystinuria. 112 32

Deficiency of cystathionine beta-synthase (CBS) causes the most common form of inherited homocystinuria. We developed a simple CBS expression system in E. coli to screen for pathogenic mutations in affected individuals. Portions of patient cDNAs were amplified by PCR and used to replace the corresponding segments of normal human CBS cDNA in the bacterial expression plasmid pHCS3. Hybrid CBS was expressed in E. coli and the segments of patient's cDNA which extinguished CBS activity were sequenced to identify the mutation. The first study of a pyridoxine-responsive patient using this screen revealed that of the clones which contained either the middle or the 3'-portion of his cDNA, about half were devoid of catalytic activity. Subsequent sequencing of the affected segments confirmed a compound heterozygosity for a maternal T833-->C transition (I278T) and for a paternal A-->C transversion in the intron 11 splice acceptor. The latter mutation leads to an in-frame deletion of exon 12 (nt 1224-1358, amino acids W408 to G453). This bacterial expression system proved to be a rapid screening method for localizing pathogenic mutations in CBS, allowing us to sequence the affected portions of mutant cDNA within 7-10 days of harvesting cultured fibroblasts.
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PMID:Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency. 130 Nov 98


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