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)

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 human gene for cystathionine beta-synthase (CBS), the enzyme deficient in classical homocystinuria, has been assigned to the subtelomeric region of band 21q22.3 by in situ hybridization of a rat cDNA probe to structurally rearranged chromosomes 21. The homologous locus in the mouse (Cbs) was mapped to the proximal half of mouse chromosome 17 by Southern analysis of Chinese hamster X mouse somatic cell hybrid DNA. Thus, CBS/Cbs and the gene for alpha A-crystalline (CRYA1/Crya-1 or Acry-1) form a conserved linkage group on human (HSA) chromosome region 21q22.3 and mouse (MMU) chromosome 17 region A-C. Features of Down syndrome (DS) caused by three copies of these genes should not be present in mice trisomic for MMU 16 that have been proposed as animal models for DS. Mice partially trisomic for MMU 16 or MMU 17 should allow gene-specific dissection of the trisomy 21 phenotype.
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PMID:The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17. 289 61

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

Twenty-nine amino acids were analyzed in the sera of 105 adult Senegambian goitrous patients classified as stages I, II, and III according to World Health Organization recommendations. Mean serum concentration of all essential amino acids revealed highly significant drops (p less than 0.001) as goiter stage increased, except for methionine (Met). Most nonessential amino acids (NEAA) and intermediary metabolites were similarly characterized by a general decrease to the subnormal range, although some resisted depression in stages II and III. Homocystine (Hcy) demonstrated a unique pattern in that it was the only NEAA distinguished by regularly rising serum levels. These data are consistent with the view that endemic goiter is associated with overall stepwise downregulation in protein metabolism. In addition to iodine restriction, generalized malnutrition may aggravate the goitrogenic processes. Serum levels of Met and Hcy strongly suggest that the first step of the transsulfuration pathway is impaired in protein-depleted states due to cystathionine beta-synthase (EC 4.2.1.22) deficiency.
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PMID:Nutritional significance of alterations in serum amino acid patterns in goitrous patients. 308 Aug 69

We measured protein-bound plasma homocyst(e)ine in 15 normal adult subjects and nine heterozygotes for homocystinuria due to cystathionine beta-synthase deficiency. The mean (+/- SD) concentrations obtained in the two groups of subjects were 4.35 +/- 1.50 and 9.16 +/- 3.40 mumoll-1, respectively. The mean values were significantly different, although the levels of three heterozygotes overlapped those of the control range. This method allows preliminary screening of the heterozygotes for homocystinuria and can be carried out by laboratories that have only facilities for amino acid analysis.
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PMID:Protein-bound plasma homocyst(e)ine and identification of heterozygotes for cystathionine-synthase deficiency. 308 21

A disturbance of serine-glycine metabolism in a group of patients who became psychotic after oral intake of serine may be due to any serine-related enzyme abnormality. In order to elucidate this problem, we studied several enzymes in fibroblasts obtained from these patients. First, the enzyme serine hydroxymethyltransferase was investigated. The apparent Km values for serine, L-tetrahydrofolate (H4folate), and pyridoxal 5'-phosphate, as well as the maximal velocities of the forward and backward reactions measured in fibroblasts obtained from patients, were not different from those in the cells from controls. We also measured the activities of another three enzymes of the folic acid cycle, viz., 5,10-methylene-H4folate dehydrogenase, 10-formyl-H4folate synthetase, and 5,10-methenyl-H4folate cyclohydrolase, as well as the enzyme cystathionine beta-synthase. Again, no differences were found among these enzymes in fibroblasts from patients and controls. It can be concluded that the psychotic symptoms occurring after the administration of serine are not the result of any malfunctioning of the enzymes investigated.
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PMID:Serine and folate metabolism in fibroblasts from episodic psychotic patients with psychedelic symptoms. 309 Oct 98

Homocysteine is an amino acid considered to cause vascular injury, arteriosclerosis, and thromboembolism. Total plasma homocysteine (free and protein-bound) was found to be twice as high in asymptomatic vitamin B12-deficient subjects (23.8 +/- 3.8 mumol/L, means +/- SEM, n = 20) as in controls (11.5 +/- 0.9 mumol/L, P less than .0001, n = 21), and higher than in heterozygotes for homocystinuria due to cystathionine beta-synthase deficiency (13.8 +/- 1.6 mumol/L, P less than .01, n = 14), who were recently shown to be much more common among patients with premature vascular disease than expected. Eight (40%) vitamin B12-deficient and two (14%) heterozygote subjects had significant homocysteinemia (greater than mean +2 SD for controls). After administration of hydroxycobalamin to vitamin B12-deficient subjects, homocysteine levels decreased to normal (-49%, 12.2 +/- 1.5 mumol/L, P less than .0001, n = 20). Thus, if homocysteine does cause vascular injury, theoretically vitamin B12-deficiency might be associated with an increased frequency of vascular disease.
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PMID:Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocystinuria due to cystathionine beta-synthase deficiency. 334 5

Three patients with homocystinuria due to cystathionine beta-synthase deficiency who developed progressive generalised dystonia are described. Although cerebrovascular thrombosis is usually thought to be responsible for neurological dysfunction in homocystinuric patients, neuropathological studies in one case and clinical and radiological evidence in the other two suggested that dystonia was not caused by brain infarction. Movement disorder associated with homocystinuria may result from the neurochemical changes in the basal ganglia related to the inherited defect in sulphur amino acid metabolism.
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PMID:Dystonia in homocystinuria. 340 94

The contents of cystathionine and taurine, as well as cystathionine beta-synthase activity, in various cerebellar regions and pineal body of normal and DL-propargylglycine-treated rats were measured. The contents of cystathionine and taurine were found to be distributed unevenly in cerebellar regions of brain of both normal and DL-propargylglycine-treated rats. The content of cystathionine in each cerebellar region and pineal body increased gradually when the dose of DL-propargylglycine was increased from 10 mg to 30 mg per 200 g body weight. On the other hand, taurine content in each cerebellar region and pineal body decreased with the administration of 30 mg of DL-propargylglycine per 200 g body weight. The contents of cystathionine and taurine were greater in the pineal body than in various cerebellar regions. The activity of cystathionine beta-synthase was also distributed unevenly in various cerebellar regions of normal rat brain, and was unaltered following treatment of rats with DL-propargylglycine.
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PMID:Contents of cystathionine and taurine in various cerebellar regions of DL-propargylglycine-treated rats. 341 43

We have developed conditions for efficient cDNA cloning of nanogram amounts of purified mRNAs coding for cystathionine beta-synthase [L-serine hydro-lyase (adding homocysteine), EC 4.2.1.22] and for the cytosolic precursors of mitochondrial ornithine transcarbamylase (carbamoylphosphate:L-ornithine carbamoyltransferase, EC 2.1.3.3) and the beta subunit of propionyl-CoA carboxylase [propanoyl-CoA: carbon-dioxide ligase (ADP-forming), EC 6.4.1.3]. The three mRNAs, prepared by sequential immunoselection from the same batch of rat liver polysomes, were pooled (20 ng each), and cDNA was synthesized by using avian reverse transcriptase. The second DNA strand was prepared by "nick-translation repair" of the cDNA . mRNA hybrid with RNase H, polymerase I, and DNA ligase from Escherichia coli. The double-stranded (ds) DNA was tailed with deoxycytidine residues, annealed with Pst I-cut/dG-tailed pBR322, and used to transform E. coli. The library generated by this three-step procedure contained 5000 independent colonies. A 550-base-pair (bp) cDNA clone of the beta subunit of propionyl-CoA carboxylase was detected by hybrid-selected translation; it was then used to screen the library for longer cDNAs. Two hybridizing cDNAs, 1200 and 1000 bp long with a 200-bp overlap, representing together a full-length copy of the coding region and 446 bp of 3' untranslated sequence, were recovered. Each plasmid mapped to the region q13.3----q22 of human chromosome 3. Cystathionine beta-synthase clones were obtained by screening the library with a single-stranded [32P]cDNA prepared directly from the highly purified synthase mRNA by reverse transcriptase. The longest hybridizing cDNA of 1700 bp was used in hybrid-selected translation and detected a polypeptide of 63 kDa, identical in size to rat liver synthase. In situ hybridization of this cDNA to q22 of human chromosome 21 confirmed two previous tentative assignments of the synthase locus to this chromosome.
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PMID:Cloning and screening with nanogram amounts of immunopurified mRNAs: cDNA cloning and chromosomal mapping of cystathionine beta-synthase and the beta subunit of propionyl-CoA carboxylase. 345 73


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