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)

High plasma total homocysteine (tHcy), low dietary intake of folate and other B vitamins, and genetic polymorphisms related to metabolism of homocysteine may interactively contribute to the risk of cardiovascular disease. We investigated whether known mutations in genes regulating homocysteine metabolism affect the responsiveness of serum folate and plasma tHcy to high intake of natural folate from food. Healthy females (n = 37) aged 22-57 y volunteered to participate in a crossover dietary intervention with two 5-wk diet periods (low and high folate diets). Concentrations of serum and RBC folate, serum vitamin B-12 and plasma tHcy were measured at baseline and at the end of each diet period. The prevalences of C677T transition of methylenetetrahydrofolate reductase (MTHFR) gene, 844ins68 of cystathionine beta-synthase (CBS) gene and A2756G mutation of methionine synthase (MS) gene were determined. Compared with the low folate diet, the high folate diet increased the serum folate concentration by 85% (P < 0.001), 77% (P < 0.001) and 55% (P < 0.05) in the subjects with the genotypes C/C (n = 19), C/T (n = 13) and T/T (n = 5), respectively, of the MTHFR gene. Also, the plasma tHcy of the subjects with the genotypes C/C, C/T and T/T was decreased by 11% (P < 0.001), 15% (P < 0.01) and 18% (P < 0.05), respectively, during the high folate diet period. The subjects carrying the G2756 allele of the MS gene (n = 15) had a more extensive reduction (P < 0.05) of plasma tHcy during the high folate diet period than the subjects with the genotype A/A (n = 22). The 844ins68 of CBS gene did not affect plasma tHcy concentrations or diet responsiveness. In conclusion, diet responsiveness of plasma homocysteine may be genetically regulated.
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PMID:Polymorphisms of key enzymes in homocysteine metabolism affect diet responsiveness of plasma homocysteine in healthy women. 1158 84

The mutations in homocysteine (Hcy) metabolism-related enzyme genes including methylenetetrahydrofolate reductase (MTHFR) C677T, cystathionine beta-synthase (CBS) 844ins68, and methionine synthase (MS) A2756G have been identified as genetic risk factors for thromboembolic events. It has been noticed that these gene mutations have heterogeneous distributions among different ethnic groups or geographic areas. The data on the prevalence of the gene mutations in Chinese population is not yet available. In the present study, we have investigated the frequency of the MTHFR C677T, CBS 844ins68, and MS A2756G mutations in 102 patients with ischemic stroke (IS), 73 patients with myocardial infarction (MI) and 100 healthy controls. The distributive frequencies of the gene variations are as follows: In the IS, MI and control groups, the mutant homozygote for MTHFR C677T is 15 (14.7%), 8 (11.7%) and 16 (16.0%), respectively, and the T allele frequency is 37.7%, 33.6% and 39.5%, respectively; the heterozygote for CBS 844ins68 is 1 (1.0%), 1 (1.4%) and 5 (5.0%), respectively; the heterozygote for MS A2756G is 18 (17.6%), 14 (19.2%) and 17 (17.0%), and the G allele frequency is 8.8%, 11.0% and 9.5%, respectively. The carrier of both MS A2756G and MTHFR C677T (combined mutations) is 14 (12.7%), 8(11.0%) and 12(12.0%), respectively. There is no statistically significant difference between the patient groups and the control group in the frequencies of these single mutation or combined mutations. The heterozygosity of CBS 844ins68 yields an odds ratio (OR) of 0.19 (95% confidence interval (CI) 0.02-1.43) for IS and 0.26 (95% CI 0.03-2.31) for MI. The T allele of MTHFR C677T yields an OR of 0.93 for IS (95% CI 0.62-1.39) and 0.77 for MI (95% CI 0.50-1.21). The G allele of MS A2756G yields an OR of 0.92(95% CI 0.47-1.81) for IS and 1.17 (95% CI 0.58-2.37) for MI. Our results suggest that neither single mutation nor combined mutations in MTHFR C677T, CBS 844ins68 and MS A2756G represent an independent risk factor for increasing IS and coronary artery disease risks in Chinese population. However, CBS 844ins68 may be a protective factor against vascular thromboembolic disease. The prevalence of CBS 844ins68 and MS A2756G in Chinese population is obviously lower than in Western Caucasian population.
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PMID:Gene polymorphisms of homocysteine metabolism-related enzymes in Chinese patients with occlusive coronary artery or cerebral vascular diseases. 1167 61

Aberrant DNA methylation is recognized as being a common feature of human neoplasia.CpG island hypermethylation and global genomic hypomethylation occur simultaneously in the cancer cell. However, very little is known about the interindividual inherited susceptibility to these epigenetic processes. To address this matter, we have genotyped in 233 cancer patients (with colorectal, breast, or lung tumors), four germ-line variants in three key genes involved in the metabolism of the methyl group, methylene-tetrahydrofolate reductase, methionine synthase, and cystathionine beta-synthase, and analyzed their association with DNA methylation parameters. The epigenetic features analyzed were the 5-methylcytosine content in the genome of the tumors and their normal counterparts, and the presence of CpG island hypermethylation of tumor suppressor genes (p16(INK4a), p14(ARF), hMLH1, MGMT, APC, LKB1, DAPK, GSTP1, BRCA1, RAR beta 2, CDH1, and RASSF1). Two positive associations were found. First, carriers of genotypes containing the methylene-tetrahydrofolate reductase 677T allele show constitutive low levels of 5-methylcytosine in their genomes (P = 0.002), and tumors in these patients do not achieve severe degrees of global hypomethylation (P = 0.047). Second, tumors occurring in homozygous carriers of the methionine synthase 2756G allele show a lower number of hypermethylated CpG islands of tumor suppressor genes (P = 0.029). The existence of these associations may provide another example of the interplay between genetic and epigenetic factors in the cancer cell.
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PMID:Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumors. 1215 64

Asian Indians who have settled overseas and those in urban India have increased risk of coronary events. Reasons for this increased risk are thought to be genetic but are yet unclear. Advances in molecular cardiology have revealed a number of single nucleotide polymorphisms associated with atherosclerosis. In this review, gene polymorphisms that have been associated with coronary diseases among Indians are discussed. Topics include the genes involved in hyperlipidemia, hypertension, and homocysteine. Mutations in the low-density lipoprotein receptor (LDLR) gene resulting in familial hypercholesterolemia have strong association with premature atherosclerosis. Common polymorphism of the apolipoproteins (apo) B-100 and E genes have been associated with variation in lipid and lipoprotein levels. Recently identified polymorphisms in the apoC3 (T-455C, C-482T), and cholesteryl ester transfer protein (CETP) (B1/B2 allele) genes are associated with increased triglycerides and reduced high-density lipoprotein (HDL)-levels, a feature now also common among Asian Indians. Angiotensin-converting enzyme-deletion (DD) polymorphism has been shown to influence beta-blocker therapy in heart failure. Mutations in methylenetetrahydrofolate reductase (C667T), cystathionine beta-synthase (T833C), and methionine synthase (A2756G) genes cause hyperhomocysteinemia, an independent risk factor for atherothrombosis. As the genetics of atherosclerosis continues to evolve, these factors along with the newer emerging factors may become a part of the routine assessment, aiding prediction of future coronary events.
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PMID:Gene polymorphism and coronary risk factors in Indian population. 1247 35

A modestly elevated total plasma homocysteine concentration (tHcy) is generally accepted as an independent and graded risk factor for various pathologies, including vascular diseases, neural tube defects, Alzheimer disease, and pregnancy complications. We analyzed 5 common functional polymorphisms in enzymes involved in homocysteine metabolism (ie, methylenetetrahydrofolate reductase [MTHFR] 677C>T and 1298A>C, methionine synthase [MTR] 2756A>G, cystathionine beta-synthase [CBS] 844ins68, and methionine synthase reductase [MTRR] 66A>G) in 452 young adults, and quantified their independent and interactive effects on tHcy concentrations. Serum folate, red cell folate, vitamin B(12), and tHcy concentrations were significantly influenced by MTHFR 677C>T genotypes. A particularly strong interaction was observed between the MTHFR 677TT genotype and serum folate, which led to a high tHcy phenotype that was more pronounced in males. The genetic contribution to the variance in tHcy was estimated to be approximately 9%, compared with approximately 35% that could be attributed to low folate and vitamin B(12). Our study indicates that dietary factors are centrally important in the control of tHcy levels in young adults with additional, but somewhat weaker, genetic effects. These data underscore the potential benefits that may be gained by improving the dietary status of young adults, and provide support for the implementation of folate/B-vitamin food fortification programs.
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PMID:Genetic and nutritional factors contributing to hyperhomocysteinemia in young adults. 1264 43

Vitamins B12, B6, and folic acid converge at the homocysteine metabolic junction where they support the activities of two key enzymes involved in intracellular homocysteine management, methionine synthase (MS) and cystathionine beta-synthase. The molecular mechanism for the regulation of homocysteine metabolism by B12 supplementation has been investigated in this study. B12 supplementation does not alter mRNA or protein turnover rates but induces translational up-regulation of MS by shifting the mRNA from the ribonucleoprotein to the polysome pool. The B12-responsive element has been localized by deletion analysis using a reporter gene assay to a 70-bp region located at the 3' end of the 5'-untranslated region of the MS mRNA. The cellular consequence of the B12 response is a 2- and 3.5-fold increase in the flux of homocysteine through the MS-dependent transmethylation pathway in HepG2 and 293 cells, respectively. It is speculated that B12-induced up-regulation of MS may have evolved as an adaptive strategy for rapidly sequestering an essential and rare nutrient whose availability may have been limited in the evolutionary history of mammals, a problem that is exacerbated by the absence of this vitamin from the plant kingdom.
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PMID:Nutritional modulation of gene expression and homocysteine utilization by vitamin B12. 1267 Sep 34

In this study, the phosphoproteome of Corynebacterium glutamicum, an industrially important soil bacterium of the Corynebacterium/Mycobacterium/Nocardia (CMN) group of Gram-positive bacteria, was investigated by two different detection methods: first, by in vivo radio-labeling using [(33)P]-phosphoric acid with subsequent autoradiography and second, by immunostaining with phosphoamino acid-specific monoclonal antibodies. After two-dimensional gel electrophoresis (2-DE), around 60 [(33)P]-labeled protein spots were visualized and around 90 antibody-decorated protein spots detected; 31 of the protein spots were detected with both methods. By peptide mass fingerprinting, 41 different proteins were identified, namely 5-enolpyruvylshikimate 3-phosphate synthase, aconitase, acyl-CoA carboxylase, acyl-CoA synthetase, ATP (synthase alpha- and beta-chain), carbamoyl-phosphate synthase, citrate synthase, cysteine synthase, DnaK, the elongation factors G, P, Ts and Tu, enolase, fructose bisphosphate aldolase, fumarase, Gap dehydrogenase, glutamine synthetase I, glycine hydroxymethyltransferase, GroEL2, GTPase, heat-inducible transcriptional repressor DnaJ2, inorganic pyrophosphatase, isocitrate dehydrogenase, ketol-acid reductoisomerase, lactate dehydrogenase, leucine-tRNA ligase, lipoamide dehydrogenase, methionine synthase, O-acetylhomoserine sulfhydrylase, pyruvate carboxylase, pyruvate kinase, pyruvate oxidase, ribosomal protein S1, RNA polymerase (beta-subunit), succinyl-CoA:CoA transferase, transketolase and UDP-N-acetylmuramoyl-L-alanine ligase, besides a hypothetical 35k protein and a hypothetical glucose kinase. Both detection techniques were used to create a phosphoproteome map. Additionally, the influence of nitrogen deprivation on the phosphoproteome of C. glutamicum was investigated.
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PMID:Towards a phosphoproteome map of Corynebacterium glutamicum. 1292 88

Epidemiologic and mechanistic evidence suggests that folate is involved in colorectal neoplasia. Some polymorphic genes involved in folate metabolism--methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), cystathionine beta-synthase (CBS exon 8, 68-base-pair insertion), and thymidylate synthase (TS enhancer region and 3' untranslated region)--have been investigated in colorectal neoplasia. For MTHFR C677T and A1298C, the variant allele is associated with reduced enzyme activity in vitro. For the other polymorphisms, functional data are limited and/or inconsistent. Genotype frequencies for all of the polymorphisms show marked ethnic and geographic variation. In most studies, MTHFR 677TT (10 studies, >4,000 cases) and 1298CC (four studies, >1,500 cases) are associated with moderately reduced colorectal cancer risk. In four of five genotype-diet interaction studies, 677TT subjects who had higher folate levels (or a "high-methyl diet") had the lowest cancer risk. In two studies, 677TT homozygote subjects with the highest alcohol intake had the highest cancer risk. Findings from six studies of MTHFR C677T and adenomatous polyps are inconsistent. There have been only one or two studies of the other polymorphisms; replication is needed. Overall, the roles of folate-pathway genes, folate, and related dietary factors in colorectal neoplasia are complex. Research priorities are suggested.
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PMID:Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a HuGE review. 1497 39

Homocysteine (Hcy) is a sulfur-containing amino acid produced when methionine is demethylated. The majority of Hcy undergoes transsulfuration to cysteine by cystathionine beta-synthase (CBS), of which vitamin B6 (pyridoxine) is an essential cofactor. The remainder of Hcy is remethylated by methionine synthase (MS), of which vitamin B12 (cobalamin) is an essential cofactor along with methylenetetrahydrofolate (MTHF). MTHF is generated by the enzyme MTHFR-reductase (MTHFR). High levels of Hcy can result from a variety of aquired factors (deficiency of vitamins B6, B12 and folic acid, high meat diet, smoking and others) or genetic (abnormalities of methionine--homocysteine metabolism). Hyperhomocysteinemia is associated with premature atherosclerosis and venous thromboembolism; so called "cholesterol of XXI. age". Results of many studies suggest that hyperhomocysteinemia, homozygous state for MTHFR gene mutation, folate deficiency are probably risk factors for recurrent fetal loss, intrauterine fetal death, thrombo-embolic disease in pregnancy, neural tube defects and congenital cardiac malformation at infants and other placental diseases (pre-eclampsia, placental abruption and intrauterine growth restriction IUGR). Those irregularities are very interesting and important for obstetricians and gynecologists. The plasma homocysteine values can be modulated by vitamins, vitamin B6 and folic acid in particular. The potential for research and possible prevention in this area is immense.
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PMID:[Hyperhomocysteinemia and pregnancy complications]. 1518 72

The hepatic enzyme glycine N-methyltransferase (GNMT) plays a major role in the control of methyl group and homocysteine metabolism. Because disruption of these vital pathways is associated with numerous pathologies, understanding GNMT control is important for evaluating methyl group regulation. Recently, gluconeogenic conditions have been shown to modulate homocysteine metabolism and treatment with glucocorticoids and/or all-trans-retinoic acid (RA)-induced active GNMT protein, thereby leading to methyl group loss. This study was conducted to determine the effect of diabetes, alone and in combination with RA, on GNMT regulation. Diabetes and RA increased GNMT activity 87 and 148%, respectively. Moreover, the induction of GNMT activity by diabetes and RA was reflected in its abundance. Cell culture studies demonstrated that pretreatment with insulin prevented GNMT induction by both RA and dexamethasone. There was a significant decline in homocysteine concentrations in diabetic rats, owing in part to a 38% increase in the abundance of the transsulfuration enzyme cystathionine beta-synthase; treatment of diabetic rats with RA prevented cystathionine beta-synthase induction. A diabetic state also increased the activity of the folate-independent homocysteine remethylation enzyme betaine-homocysteine S-methyltransferase, whereas the activity of the folate-dependent enzyme methionine synthase was diminished 52%. In contrast, RA treatment attenuated the streptozotocin-mediated increase in betaine-homocysteine S-methyltransferase, whereas methionine synthase activity remained diminished. These results indicate that both a diabetic condition and RA treatment have marked effects on the metabolism of methyl groups and homocysteine, a finding that may have significant implications for diabetics and their potential sensitivity to retinoids.
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PMID:Modulation of methyl group metabolism by streptozotocin-induced diabetes and all-trans-retinoic acid. 1534 42


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