Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.1.22 (cystathionine beta-synthase)
 965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic gamma-cystathionase activity at 12 h after the intraperitoneal injection decreased in proportion to the amount of D,L-propargylglycine administered, but hepatic cystathionine beta-synthase activity did not change. Contents of cystathionine in the liver increased gradually from 0.25 mg to 30 mg/200 g body weight in proportion to the amounts of D,L-propargylglycine injected; in the kidney, 0.5 mg to 10 mg; in the brain, 5 mg to 20 mg; in the serum, 0.25 mg to 30 mg. Contents of N-acetylcystathionine in the liver and kidney also increased in parallel with the accumulation of cystathionine.
 ...
PMID:Effect of D,L-propargylglycine on cystathionine metabolism in rats. 647 95

Cystathionine beta-synthase, S-adenosylmethionine synthetase and cystathionase activities were assayed in skin fibroblast cultures from five pyridoxine responsive and five pyridoxine non-responsive homocystinurics, six obligate heterozygotes for homocystinuria and ten normal control subjects. The specific deficiency in cystathionine beta-synthase activity was confirmed in nine of the homocystinuric cultures. However, in one pyridoxine responsive case the level of cystathionine beta-synthase activity was found to be comparable with those of the heterozygotes. A negative correlation appeared to exist between the level of residual enzyme activity and the pre-treatment severity of clinical symptoms.
 ...
PMID:Homocystinuria: studies on cystathionine beta-synthase, S-adenosylmethionine synthetase and cystathionase activities in skin fibroblasts. 678 21

The contribution of cystathionine gamma-lyase, cystathionine beta-synthase and cysteine aminotransferase coupled to 3-mercaptopyruvate sulphurtransferase to cysteine desulphhydration in rat liver and kidney was assessed with four different assay systems. Cystathionine gamma-lyase and cystathionine beta-synthase were active when homogenates were incubated with 280 mM-L-cysteine and 3 mM-pyridoxal 5'-phosphate at pH 7.8. Cysteine aminotransferase in combination with 3-mercaptopyruvate sulphurtransferase catalysed essentially all of the H2S production from cysteine at pH 9.7 with 160 mM-L-cysteine, 2 mM-pyridoxal 5'-phosphate, 3 mM-2-oxoglutarate and 3 mM-dithiothreitol. At more-physiological concentrations of cysteine (2 mM) cystathionine gamma-lyase and cystathionine beta-synthase both appeared to be active in cysteine desulphhydration, whereas the aminotransferase pathway did not. The effect of inhibition of cystathionine gamma-lyase by a suicide inactivator, propargylglycine, in the intact rat was also investigated; there was no significant effect of propargylglycine administration on the urinary excretion of total 35S, 35SO4(2-) or [35S]taurine formed from labelled dietary cysteine.
 ...
PMID:Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat. 715 Feb 44

Developmental changes in the activities of cystathionine beta-synthase and cystathionine gamma-lyase were measured in six regions of rat brain. On day-1, no differences were observed in the activities of cystathionine beta-synthase and cystathionine gamma-lyase among these regions, the values being about 40 nmol/h/mg protein, and 3 nmol/h/mg protein, respectively. Cystathionine beta-synthase activity increased gradually during development at almost the same rate in each region, reaching the adult level at week-4 (about 4-fold). Cystathionine gamma-lyase activity also increased during development, reaching adult level at week-2. But, the increase of enzyme activity in the cerebellum (about 1.8-fold) was clearly lower than that in the other regions (about 4-fold). Cystathionine gamma-lyase content in the various regions of week-3 rat brain estimated by immunoblotting was consistent with the enzyme activity, and the enzyme level in the cerebellum was lower than that in the other regions. Cystathionine content of cerebellum in week-3 increased rapidly during development, and was about five-fold more than that on day-1. However, cystathionine content in the other regions did not change during development. These findings indicated that at least one reason of the high content of cystathionine in the 3 weeks rat cerebellum was due to the low level of cystathionine gamma-lyase.
 ...
PMID:Changes in cystathionine gamma-lyase in various regions of rat brain during development. 749 71

Rats fed with a vitamin B6-deficient 70% casein diet for 5 weeks were found to have decreased considerably in the content of phosphatidylcholine (PC) in liver microsomes, presumably because of the depressed PC biosynthesis from choline or phosphatidylethanolamine (PE). The activities of choline phosphokinase and choline phosphotransferase in liver decreased, apparently, as compared with the pair-fed control or control rats. The hepatic level of the PE methyltransferase co-substrate, S-adenosylmethionine (SAM), decreased about 1/3, but the level of the inhibitory metabolite, S-adenosylhomocysteine (SAH), was elevated due to the marked reduction in the activities of cystathionine beta-synthase and gamma-cystathionase. The resultant molar ratio of SAM/SAH decreased drastically such that the methylation of PE to PC was decreased in vivo, as confirmed by lowering the activity of PE methyltransferase in vitro in response to a decreased molar ratio of SAM/SAH. A similar effect on the PE methylation was also observed in the pair-fed control rats, but the PC biosynthesis from choline clearly compensated for the drop of PC biosynthesis from PE. Results of this study demonstrate that vitamin B6 deficiency modified methionine metabolism and decreased choline utilization, and thus indirectly affected the biosynthesis of PC in liver microsomes.
 ...
PMID:Alteration in the phosphatidylcholine biosynthesis of rat liver microsomes caused by vitamin B6 deficiency. 776 14

The fission yeast Schizosaccharomyces pombe has a unique organization of sulfur amino acid metabolism: it has two distinct O-acetylhomoserine sulfhydrylases (homocysteine synthases). Similar to Enterobacteriaceae, S. pombe lacks cystathionine beta-synthase and cystathionine gamma-lyase-the enzymes of the reverse transsulfuration pathway, by which methionine is readily metabolized to cysteine-a likely effector in the sulfur metabolite repression system. Consequently no repression of sulfate assimilation is observed when methionine is added to the growth medium.
 ...
PMID:Sulfur amino acid metabolism in Schizosaccharomyces pombe: occurrence of two O-acetylhomoserine sulfhydrylases and the lack of the reverse transsulfuration pathway. 792 67

Pyridoxal-5'-phosphate-dependent enzymes catalyze manifold reactions in the metabolism of amino acids. A comprehensive comparison of amino acid sequences has shown that most of these enzymes can be assigned to one of three different families of homologous proteins. The sequences of the enzymes of each family were aligned and their homology confirmed by profile analysis. Scrutiny of the reactions catalyzed by the enzymes showed that their affiliation with one of the three structurally defined families correlates in most cases with their regio-specificity. In the largest family, the covalency changes of the substrate occur at the same carbon atom that carries the amino group forming the imine linkage with the coenzyme. This family was thus named alpha family. It comprises glycine hydroxymethyltransferase, glycine C-acetyltransferase, 5-aminolevulinate synthase, 8-amino-7-oxononanoate synthase, all aminotransferases (with the possible exception of subgroup III), a number of other enzymes relatively closely related with the aminotransferases and very likely a certain group of amino acid decarboxylases as well as tryptophanase and tyrosine phenol-lyase which, however, catalyze beta-elimination reactions. The beta family includes L- and D-serine dehydratase, threonine dehydratase, the beta subunit of tryptophan synthase, threonine synthase and cysteine synthase. These enzymes catalyze beta-replacement or beta-elimination reactions. The gamma family incorporates O-succinylhomoserine (thiol-lyase, O-acetylhomoserine (thiol)-lyase, and cystathionine gamma-lyase, which catalyze gamma-replacement or gamma-elimination reactions, as well as cystathionine beta-lyase. The alpha and gamma family might be distantly related with one another, but are clearly not homologous with the beta family. Apparently, the primordial pyridoxal-5'-phosphate-dependent enzymes were regio-specific catalysts, which first specialized for reaction specificity and then for substrate specificity. The following pyridoxal-5'-phosphate-dependent enzymes seem to be unrelated with the alpha, beta or gamma family by the criterion of profile analysis:alanine racemase, selenocysteine synthase, and many amino acid decarboxylases. These enzymes may represent yet other families of B6 enzymes.
 ...
PMID:Evolutionary relationships among pyridoxal-5'-phosphate-dependent enzymes. Regio-specific alpha, beta and gamma families. 811 47

The transsulfuration pathways allow the interconversion of homocysteine and cysteine with the intermediary formation of cystathionine. The various organisms studied up to now incorporate reduced sulfur into a three- or a four-carbon chain and use differently the transsulfuration pathways to synthesize sulfur amino acids. In enteric bacteria, the synthesis of cysteine is the first step of organic sulfur metabolism and homocysteine is derived from cysteine. Fungi are capable of incorporating reduced sulfur into a four-carbon chain, and they possess two operating transsulfuration pathways. By contrast, synthesis of cysteine from homocysteine is the only existing transsulfuration pathway in mammals. In Saccharomyces cerevisiae, genetic, phenotypic, and enzymatic study of mutants has allowed us to demonstrate that homocysteine is the first sulfur amino acid to be synthesized and cysteine is derived only from homocysteine (H. Cherest and Y. Surdin-Kerjan, Genetics 130:51-58, 1992). We report here the cloning of genes STR4 and STR1, encoding cystathionine beta-synthase and cystathionine gamma-lyase, respectively. The only phenotypic consequence of the inactivation of STR1 or STR4 is cysteine auxotrophy. The sequencing of gene STR4 has allowed us to compare all of the known sequences of transsulfuration enzymes and enzymes catalyzing the incorporation of reduced sulfur in carbon chains. These comparisons reveal a partition into two families based on sequence motifs. This partition mainly correlates with similarities in the catalytic mechanisms of these enzymes.
 ...
PMID:Cysteine biosynthesis in Saccharomyces cerevisiae occurs through the transsulfuration pathway which has been built up by enzyme recruitment. 836 24

Homocysteine can be methylated to form methionine by the cobalamin- (Cbl) and folate-dependent enzyme, methionine synthase; serum levels of total homocysteine are elevated in greater than 95% of patients with either Cbl or folate deficiency. Homocysteine can also condense with serine to form cystathionine in a pyridoxal phosphate-dependent reaction catalyzed by cystathionine beta-synthase. Cystathionine is subsequently cleaved to cysteine and alpha-ketobutyrate by the pyridoxal phosphate-dependent enzyme gamma-cystathionase. To assess levels of cystathionine in Cbl and folate deficiency, we developed a new capillary gas chromatographic-mass spectrometric assay and measured cystathionine in the serum of normal subjects and patients with clinically confirmed deficiencies of these vitamins. The normal range for serum cystathionine was 65 to 301 nmol/L (median = 126 nmol/L) for 50 normal blood donors. In 30 patients with clinically confirmed Cbl deficiency, values for cystathionine ranged from 208 nmol/L to 2,920 nmol/L (median = 816 nmol/L) and 26 (87%) had levels above the normal range. In 20 patients with clinically confirmed folate deficiency, cystathionine concentrations ranged from 138 nmol/L to 4,150 nmol/L (median = 1,560 nmol/L) and 19 (95%) had values above the normal range. Five homozygotes for cystathionine beta-synthase deficiency had high values for serum-total homocysteine and low or low-normal values for serum cystathionine that ranged from 30 nmol/L to 114 nmol/L even though they were on treatment with pyridoxine and had partially responded. One patient with a defect in the synthesis of 5-CH3-tetrahydrofolate and five patients with defects in the synthesis of CH3-Cbl had high values for serum-total homocysteine and high values for cystathionine that ranged from 311 nmol/L to 1,500 nmol/L even though they were on treatment with folic acid and Cbl, respectively, and had partially responded. We conclude that levels of cystathionine are evaluated in the serum of most patients with Cbl and folate deficiency and that they are useful in the differential diagnosis of an elevated serum-total homocysteine level.
 ...
PMID:Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. 850 76

The effect of concentrations of sulfur-containing amino acids, activities of cystathionine gamma-lyase and cystathionine beta-synthase, and level of vitamin B6 were examined following menthionine administration in normal rats and chronically uremic rats with 7/8 nephrectomy. In the uremic rats, the serum levels of methionine, cystathionine, cysteine and taurine increased in proportion to the amounts of methionine administered. The increase of taurine content in the serum and liver was particularly marked. Cystathionine beta-synthase activity in the liver increased with the administration, but the serum level of pyridoxal phosphate decreased markedly. The body weight gain of rats decreased with the administration, and the contents of urea and creatinine in serum increased. Thus, vitamin B6 deficiency in chronically uremic rats administered with large amounts of methionine may reduce growth, lower renal function and cause abnormal metabolism of sulfur-containing amino acids.
 ...
PMID:Content of sulfur amino acids and vitamin B6 and related enzyme activities in rats with chronic renal failure fed a high methionine diet. 888 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>