betaine homocysteine methyltransferase


Gene Symbol: betaine homocysteine methyltransferase
Description: betaine--homocysteine S-methyltransferase
Alias: BHMT1, HEL-S-61p, betaine--homocysteine S-methyltransferase 1, epididymis secretory sperm binding protein Li 61p
Species: human

Top Publications

  1. Terruzzi I, Senesi P, Fermo I, Lattuada G, Luzi L. Are genetic variants of the methyl group metabolism enzymes risk factors predisposing to obesity?. J Endocrinol Invest. 2007;30:747-53 pubmed
  2. Castro C, Millian N, Garrow T. Liver betaine-homocysteine S-methyltransferase activity undergoes a redox switch at the active site zinc. Arch Biochem Biophys. 2008;472:26-33 pubmed publisher
    ..Experiments using the glutamate-cysteine ligase modifier subunit knockout mice Gclm(-/-), which are severely impaired in glutathione synthesis, show that BHMT activity is reduced about 75% in Gclm(-/-) compared to Gclm(+/+) mice. ..
  3. Pellanda H, Namour F, Fofou Caillierez M, Bressenot A, Alberto J, Chery C, et al. A splicing variant leads to complete loss of function of betaine-homocysteine methyltransferase (BHMT) gene in hepatocellular carcinoma. Int J Biochem Cell Biol. 2012;44:385-92 pubmed publisher
    ..Whether this abnormal transcription of BHMT is part or consequence of liver carcinogenesis should deserve further investigations...
  4. Weisberg I, Park E, Ballman K, Berger P, Nunn M, Suh D, et al. Investigations of a common genetic variant in betaine-homocysteine methyltransferase (BHMT) in coronary artery disease. Atherosclerosis. 2003;167:205-14 pubmed
  5. Boyles A, Billups A, Deak K, Siegel D, Mehltretter L, Slifer S, et al. Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions. Environ Health Perspect. 2006;114:1547-52 pubmed
  6. Feng Q, Kalari K, Fridley B, Jenkins G, Ji Y, Abo R, et al. Betaine-homocysteine methyltransferase: human liver genotype-phenotype correlation. Mol Genet Metab. 2011;102:126-33 pubmed publisher
    ..These observations may help us to understand individual variation in the regulation of BHMT in the human liver and its possible relationship to variation in methylation. ..
  7. Lawrance A, Racine J, Deng L, Wang X, Lachapelle P, Rozen R. Complete deficiency of methylenetetrahydrofolate reductase in mice is associated with impaired retinal function and variable mortality, hematological profiles, and reproductive outcomes. J Inherit Metab Dis. 2011;34:147-57 pubmed publisher
    ..In addition, our novel findings of decreased spleen weights, thrombocytopenia, and impaired retinal function warrant investigation in patients with severe MTHFR deficiency or other forms of homocystinuria. ..
  8. Wang P, Wu T, Schwender H, Wang H, Shi B, Wang Z, et al. Evidence of interaction between genes in the folate/homocysteine metabolic pathway in controlling risk of non-syndromic oral cleft. Oral Dis. 2018;24:820-828 pubmed publisher
  9. de Queiroz J, Vieira J, de Oliveira G, Braga C, da Cunha Bataglioli I, da Silva J, et al. Identification of Biomarkers of Mercury Contamination in Brachyplatystoma filamentosum of the Madeira River, Brazil, Using Metalloproteomic Strategies. Biol Trace Elem Res. 2019;187:291-300 pubmed publisher

More Information

Publications144 found, 100 shown here

  1. Xu J, Wang F, Jakovlić I, Prisingkorn W, Li J, Wang W, et al. Metabolite and gene expression profiles suggest a putative mechanism through which high dietary carbohydrates reduce the content of hepatic betaine in Megalobrama amblycephala. Metabolomics. 2018;14:94 pubmed publisher
    ..However, betaine supplementation may have caused a temporary disruption in the metabolic homeostasis. ..
  2. Na J, Choi Y, Jun D, Kim Y. Alleviation of paraquat-induced oxidative lung injury by betaine via regulation of sulfur-containing amino acid metabolism despite the lack of betaine-homocysteine methyltransferase (BHMT) in the lung. Food Funct. 2019;10:1225-1234 pubmed publisher
    ..The results suggest that betaine may enhance pulmonary antioxidant capacity by modulating the metabolism of sulfur-containing amino acids and related substances despite the lack of BHMT in the lung. ..
  3. Ong J, Woo J, Hiong K, Ching B, Wong W, Chew S, et al. Molecular characterization of betaine-homocysteine methyltransferase 1 from the liver, and effects of aestivation on its expressions and homocysteine concentrations in the liver, kidney and muscle, of the African lungfish, Protopterus annectens. Comp Biochem Physiol B Biochem Mol Biol. 2015;183:30-41 pubmed publisher
    ..This study aimed to determine homocysteine concentrations, and mRNA expression levels and protein abundances of bhmt1/Bhmt1 in the liver, kidney and muscle of the African lungfish, Protopterus annectens, during the induction (6 days)..
  4. Mills J, Carter T, Kay D, Browne M, Brody L, Liu A, et al. Folate and vitamin B12-related genes and risk for omphalocele. Hum Genet. 2012;131:739-46 pubmed publisher
    ..Our data, if confirmed, suggest that supplements containing both folic acid and vitamin B12 may be beneficial in preventing omphaloceles. ..
  5. Lu X, Zhang H, Yang G, Li M, Chen J. Comparative transcriptome analysis on the alteration of gene expression in ayu (Plecoglossus altivelis) larvae associated with salinity change. Dongwuxue Yanjiu. 2016;37:126-35 pubmed
    ..Our data indicate that FW acclimation reduced the growth rate of ayu larvae, which might result from the expression alteration of genes related to endocrine hormones, energy metabolism, and direct osmoregulation. ..
  6. Zhang Q, White H. Short communication: The effect of increasing concentrations of different methionine forms and 2-hydroxy-4-(methylthio)butanoic acid on genes controlling methionine metabolism in primary bovine neonatal hepatocytes. J Dairy Sci. 2019;102:866-870 pubmed publisher
    ..The lack of differences among Met forms on regulating genes examined indicates that all Met forms similarly reduced genes controlling Met regeneration and metabolism in primary bovine hepatocytes. ..
  7. Ueland P. Choline and betaine in health and disease. J Inherit Metab Dis. 2011;34:3-15 pubmed publisher
    ..Thus, choline and betaine showed opposite relations with key components of metabolic syndrome, suggesting a disruption of mitochondrial choline oxidation to betaine as part of the mitochondrial dysfunction in metabolic syndrome. ..
  8. Ndisang J. The heme oxygenase system selectively modulates proteins implicated in metabolism, oxidative stress and inflammation in spontaneously hypertensive rats. Curr Pharm Des. 2014;20:1318-27 pubmed
    ..Collectively, these findings underscore the pleiotropic effects of the HO-system in cellular homeostasis with important roles in metabolism and defence. ..
  9. Moore J, Hubler S, Nelson C, Nashold F, Spanier J, Hayes C. 1,25-Dihydroxyvitamin D3 increases the methionine cycle, CD4+ T cell DNA methylation and Helios+Foxp3+ T regulatory cells to reverse autoimmune neurodegenerative disease. J Neuroimmunol. 2018;324:100-114 pubmed publisher
    ..It also rapidly increased CD4+ T cell Bhmt1 transcripts, betaine:homocysteine methyltransferase-1 (BHMT1) enzyme activity, and global DNA methylation...
  10. Chi L, Xue J, Tu P, Lai Y, Ru H, Lu K. Gut microbiome disruption altered the biotransformation and liver toxicity of arsenic in mice. Arch Toxicol. 2019;93:25-35 pubmed publisher
    ..GM disruption also increases the toxic effects of As and may increase the risk of As-induced HCC in mice. ..
  11. Xu L, Huang D, Hu Q, Wu J, Wang Y, Feng J. Betaine alleviates hepatic lipid accumulation via enhancing hepatic lipid export and fatty acid oxidation in rats fed with a high-fat diet. Br J Nutr. 2015;113:1835-43 pubmed publisher
    ..The results suggest that betaine administration enhanced hepatic lipid export and fatty acid oxidation in high-fat diet-fed rats, thus effectively alleviating fat accumulation in the liver. ..
  12. Rui Y, Xu Z, Chen Z, Zhang S. The GST-BHMT assay reveals a distinct mechanism underlying proteasome inhibition-induced macroautophagy in mammalian cells. Autophagy. 2015;11:812-32 pubmed publisher
  13. Li X, Sun Q, Li X, Cai D, Sui S, Jia Y, et al. Dietary betaine supplementation to gestational sows enhances hippocampal IGF2 expression in newborn piglets with modified DNA methylation of the differentially methylated regions. Eur J Nutr. 2015;54:1201-10 pubmed publisher
  14. Costa I, Thompson J, Ortega J, Prosdocimi F. Metazoan remaining genes for essential amino acid biosynthesis: sequence conservation and evolutionary analyses. Nutrients. 2014;7:1-16 pubmed publisher
  15. Sim W, Yin H, Choi H, Choi Y, Kwak H, Kim S, et al. L-serine supplementation attenuates alcoholic fatty liver by enhancing homocysteine metabolism in mice and rats. J Nutr. 2015;145:260-7 pubmed publisher
    ..0% and 30.6%, respectively, compared with the ethanol group. Silencing betaine homocysteine methyltransferase, cystathionine β-synthase, or methionine increased intracellular homocysteine and TG ..
  16. Idriss A, Hu Y, Hou Z, Hu Y, Sun Q, Omer N, et al. Dietary betaine supplementation in hens modulates hypothalamic expression of cholesterol metabolic genes in F1 cockerels through modification of DNA methylation. Comp Biochem Physiol B Biochem Mol Biol. 2018;217:14-20 pubmed publisher
    ..These results indicate that feeding betaine to hens modulates hypothalamic expression of genes involved in cholesterol metabolism and brain functions in F1 cockerels with modification of promoter DNA methylation. ..
  17. Dupuy C, Galland C, Pichereau V, Sanchez W, Riso R, Labonne M, et al. Assessment of the European flounder responses to chemical stress in the English Channel, considering biomarkers and life history traits. Mar Pollut Bull. 2015;95:634-45 pubmed publisher
    ..Flounder life history traits were analyzed by otolith microchemistry, in order to depict how the fish use their habitat and thus respond to chemical stress in estuaries. ..
  18. Brekhman V, Malik A, Haas B, Sher N, Lotan T. Transcriptome profiling of the dynamic life cycle of the scypohozoan jellyfish Aurelia aurita. BMC Genomics. 2015;16:74 pubmed publisher
    ..It highlights the importance of numerous stage-specific transcription factors in driving morphological and functional changes throughout this complex metamorphosis, and is expected to be a valuable resource to the community. ..
  19. Ganu R, Ishida Y, Koutmos M, Kolokotronis S, Roca A, Garrow T, et al. Evolutionary Analyses and Natural Selection of Betaine-Homocysteine S-Methyltransferase (BHMT) and BHMT2 Genes. PLoS ONE. 2015;10:e0134084 pubmed publisher
    ..The dN/dS ratios in both BHMT and BHMT2 was highest following the gene duplication, suggesting that purifying selection played a lesser role as the two paralogs diverged in function. ..
  20. Zhou Y, Zhou Z, Batistel F, Martínez Cortés I, Pate R, Luchini D, et al. Methionine and choline supply alter transmethylation, transsulfuration, and cytidine 5'-diphosphocholine pathways to different extents in isolated primary liver cells from dairy cows. J Dairy Sci. 2018;101:11384-11395 pubmed publisher
    ..The relevance of these data in vivo merit further study. ..
  21. Hou Z, Sun Q, Hu Y, Yang S, Zong Y, Zhao R. Maternal betaine administration modulates hepatic type 1 iodothyronine deiodinase (Dio1) expression in chicken offspring through epigenetic modifications. Comp Biochem Physiol B Biochem Mol Biol. 2018;218:30-36 pubmed publisher
  22. Nembhard W, Tang X, Hu Z, Macleod S, Stowe Z, Webber D. Maternal and infant genetic variants, maternal periconceptional use of selective serotonin reuptake inhibitors, and risk of congenital heart defects in offspring: population based study. BMJ. 2017;356:j832 pubmed publisher
  23. Gupta S, Wang L, Kruger W. Betaine supplementation is less effective than methionine restriction in correcting phenotypes of CBS deficient mice. J Inherit Metab Dis. 2016;39:39-46 pubmed publisher
    ..Our findings indicate that while betaine supplementation does have some beneficial effects, it is not as effective as methionine restriction for reversing the phenotypes associated with severe CBS deficiency in mice. ..
  24. Jia Y, Song H, Gao G, Cai D, Yang X, Zhao R. Maternal Betaine Supplementation during Gestation Enhances Expression of mtDNA-Encoded Genes through D-Loop DNA Hypomethylation in the Skeletal Muscle of Newborn Piglets. J Agric Food Chem. 2015;63:10152-60 pubmed publisher
    ..05). These results suggest that maternal betaine supplementation during gestation enhances expression of mtDNA-encoded genes through D-loop DNA hypomethylation in the skeletal muscle of newborn piglets. ..
  25. Park E, Garrow T. Interaction between dietary methionine and methyl donor intake on rat liver betaine-homocysteine methyltransferase gene expression and organization of the human gene. J Biol Chem. 1999;274:7816-24 pubmed
  26. Shaw G, Lu W, Zhu H, Yang W, Briggs F, Carmichael S, et al. 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects. BMC Med Genet. 2009;10:49 pubmed publisher
    ..Our observations do not implicate a particular folate transport or metabolism gene to be strongly associated with risks for spina bifida or conotruncal defects. ..
  27. Chmurzynska A, Mlodzik M, Radziejewska A, Szwengiel A, Malinowska A, Nowacka Woszuk J. Caloric restriction can affect one-carbon metabolism during pregnancy in the rat: A transgenerational model. Biochimie. 2018;152:181-187 pubmed publisher
    ..001). Food deprivation may affect one-carbon metabolism in pregnant rats, but it does not stimulate persistent metabolic changes that can be observed during the pregnancy of their progeny of the F1 or F2 generations. ..
  28. Giunti L, Buccoliero A, Pantaleo M, Lucchesi M, Provenzano A, Palazzo V, et al. Molecular characterization of paediatric glioneuronal tumours with neuropil-like islands: a genome-wide copy number analysis. Am J Cancer Res. 2016;6:2910-2918 pubmed
    ..Our work gives an important contribution in knowledge and classification of this family of tumours. ..
  29. Cornelis M, Fornage M, Foy M, Xun P, Gladyshev V, Morris S, et al. Genome-wide association study of selenium concentrations. Hum Mol Genet. 2015;24:1469-77 pubmed publisher
    ..Our findings show evidence of a genetic link between Se and Hcy pathways, both involved in cardiometabolic disease. ..
  30. Martinelli M, Masiero E, Carinci F, Morselli P, Pezzetti F, Scapoli L. New evidence for the role of cystathionine beta-synthase in non-syndromic cleft lip with or without cleft palate. Eur J Oral Sci. 2011;119:193-7 pubmed publisher
    ..This suggests that human orofacial development is influenced by CBS genotypes that possibly operate through intergenerational fetal-maternal interaction. ..
  31. Deminice R, da Silva R, Lamarre S, Kelly K, Jacobs R, Brosnan M, et al. Betaine supplementation prevents fatty liver induced by a high-fat diet: effects on one-carbon metabolism. Amino Acids. 2015;47:839-46 pubmed publisher
    ..In conclusion, the regulation of the expression of MGAT by betaine supplementation provides an additional and novel mechanism by which betaine supplementation regulates lipid metabolism and prevents accumulation of fat in the liver. ..
  32. Yan H, Li Z, Shen Q, Wang Q, Tian J, Jiang Q, et al. Aberrant expression of cell cycle and material metabolism related genes contributes to hepatocellular carcinoma occurrence. Pathol Res Pract. 2017;213:316-321 pubmed publisher
    ..Taken together, aberrant expression of cell cycle related genes (e.g., CDK1, CCNA2, CCNB1, BUB1, MAD2L1 and CDC20) and material metabolism related genes (e.g., CYP2B6, ACAA1, BHMT and ALDH2) may contribute to HCC occurrence. ..
  33. Zhang T, Wei W, Dirsch O, Krüger T, Kan C, Xie C, et al. Identification of Proteins Interacting with Cytoplasmic High-Mobility Group Box 1 during the Hepatocellular Response to Ischemia Reperfusion Injury. Int J Mol Sci. 2017;18: pubmed publisher
    ..This finding may help to better understand the cellular response to IRI in the liver and to identify novel molecular targets for reducing ischemic injury. ..
  34. Ganz A, Cohen V, Swersky C, Stover J, Vitiello G, Lovesky J, et al. Genetic Variation in Choline-Metabolizing Enzymes Alters Choline Metabolism in Young Women Consuming Choline Intakes Meeting Current Recommendations. Int J Mol Sci. 2017;18: pubmed publisher
    ..Such metabolic differences may contribute to disease pathogenesis and prognosis over the long-term. ..
  35. Fan W, Cheng J, Zhang S, Liu X. Cloning and functions of the HBxAg-binding protein XBP1. Mol Med Rep. 2013;7:618-22 pubmed publisher
  36. Zhang B, Denomme M, White C, Leung K, Lee M, Greene N, et al. Both the folate cycle and betaine-homocysteine methyltransferase contribute methyl groups for DNA methylation in mouse blastocysts. FASEB J. 2015;29:1069-79 pubmed publisher
    ..Both the folate cycle and betaine/BHMT appear to contribute to a methyl pool required for normal ICM development and establishing initial embryonic DNA methylation. ..
  37. Murray T, Dong X, Sawyer G, Caldwell A, Halket J, Sherwood R, et al. NADPH oxidase 4 regulates homocysteine metabolism and protects against acetaminophen-induced liver damage in mice. Free Radic Biol Med. 2015;89:918-30 pubmed publisher
  38. Kwak H, Kim Y, Oh S, Kim S. Sulfur amino acid metabolism in Zucker diabetic fatty rats. Biochem Pharmacol. 2015;96:256-66 pubmed publisher
    ..The present study suggests that the decrease in hepatic methionine may be responsible for the decreases in its metabolites, such as homocysteine, cysteine, and taurine in liver and consequently decreased plasma homocysteine levels. ..
  39. Sehayek E, Wang R, Ono J, Zinchuk V, Duncan E, Shefer S, et al. Localization of the PE methylation pathway and SR-BI to the canalicular membrane: evidence for apical PC biosynthesis that may promote biliary excretion of phospholipid and cholesterol. J Lipid Res. 2003;44:1605-13 pubmed
    ..A prominent protein revealed by this analysis was betaine homocysteine methyltransferase (BHMT)...
  40. Li D, Liu H, Fang Y, Huo J, Wu Q, Wang T, et al. Hyperhomocysteinemia in polycystic ovary syndrome: decreased betaine-homocysteine methyltransferase and cystathionine β-synthase-mediated homocysteine metabolism. Reprod Biomed Online. 2018;37:234-241 pubmed publisher
    ..These findings indicate that decreased liver Bhmt and Cbs-mediated homocysteine metabolism might have a role in hyperhomocysteinemia in PCOS and provides further evidence for a potential role of decreased liver function in PCOS. ..
  41. Idriss A, Hu Y, Sun Q, Jia L, Jia Y, Omer N, et al. Prenatal betaine exposure modulates hypothalamic expression of cholesterol metabolic genes in cockerels through modifications of DNA methylation. Poult Sci. 2017;96:1715-1724 pubmed publisher
    ..These results indicate that maternal betaine modulates hypothalamic cholesterol metabolism in cockerels through modifying DNA methylation on the promoter of cholesterol metabolic genes. ..
  42. Galland C, Dupuy C, Loizeau V, Danion M, Auffret M, Quiniou L, et al. Proteomic analysis of the European flounder Platichthys flesus response to experimental PAH-PCB contamination. Mar Pollut Bull. 2015;95:646-57 pubmed publisher
    ..flesus response to chemical contamination. ..
  43. Thomes P, Osna N, Bligh S, Tuma D, Kharbanda K. Role of defective methylation reactions in ethanol-induced dysregulation of intestinal barrier integrity. Biochem Pharmacol. 2015;96:30-8 pubmed publisher
    ..We also propose betaine as a potential therapeutic option for leaky gut in alcohol-consuming patients who are at the risk of developing ALD. ..
  44. Piao W, Guo J, Bao Y, Wang F, Zhang T, Huo J, et al. Analysis of polymorphisms of genes associated with folate-mediated one-carbon metabolism and neural tube defects in Chinese Han Population. Birth Defects Res A Clin Mol Teratol. 2016;106:232-9 pubmed publisher
    ..The SNPs rs2797840 and rs2073817 in SARDH may serve as an indicator for the occurrence of NTDs in the Chinese Han population, and rs2797840 may also be an indicator for folate content of brain. ..
  45. Jing M, Rech L, Wu Y, Goltz D, Taylor C, House J. Effects of zinc deficiency and zinc supplementation on homocysteine levels and related enzyme expression in rats. J Trace Elem Med Biol. 2015;30:77-82 pubmed publisher
    ..These results demonstrated that homocysteine homeostasis appeared to be disturbed by Zn deficiency but not Zn supplementation, and elevated serum homocysteine might be due to reduced expression of MS during Zn deficiency. ..
  46. Chen Y, Lin P, Hsieh C, Peng C, Peng R. The proteomic and genomic teratogenicity elicited by valproic acid is preventable with resveratrol and α-tocopherol. PLoS ONE. 2014;9:e116534 pubmed publisher
    ..Taken together, VPA elicits hemorrhagic myoliposis via these action mechanisms, and RV and vit E are effective for alleviation of such adverse effects. ..
  47. Bose N, Greenspan P, Momany C. Expression of recombinant human betaine: homocysteine S-methyltransferase for x-ray crystallographic studies and further characterization of interaction with S-adenosylmethionine. Protein Expr Purif. 2002;25:73-80 pubmed
    ..S-Adenosylmethionine (SAMe) has no effect on the recombinant BHMT's ability to methylate homocysteine nor does the enzyme appear to bind SAMe when examined by microcalorimetry. ..
  48. Jia L, Li J, He B, Jia Y, Niu Y, Wang C, et al. Abnormally activated one-carbon metabolic pathway is associated with mtDNA hypermethylation and mitochondrial malfunction in the oocytes of polycystic gilt ovaries. Sci Rep. 2016;6:19436 pubmed publisher PCO group, which was associated with significantly up-regulated one-carbon metabolic enzymes betaine homocysteine methyltransferase (BHMT), glycine N-methyltransferase (GNMT) and the DNA methyltransferase DNMT1...
  49. Ou X, Yang H, Ramani K, Ara A, Chen H, Mato J, et al. Inhibition of human betaine-homocysteine methyltransferase expression by S-adenosylmethionine and methylthioadenosine. Biochem J. 2007;401:87-96 pubmed
    ..While SAM's mechanism is NF-kappaB-dependent, MTA has both NF-kappaB-dependent and -independent mechanisms. ..
  50. Breksa A, Garrow T. Random mutagenesis of the zinc-binding motif of betaine-homocysteine methyltransferase reveals that Gly 214 is essential. Arch Biochem Biophys. 2002;399:73-80 pubmed
    ..We hypothesize that these Gly residues provide the necessary flexibility to the Zn-binding region to permit coordination of the metal. ..
  51. Mostowska A, Hozyasz K, Biedziak B, Misiak J, Jagodzinski P. Polymorphisms located in the region containing BHMT and BHMT2 genes as maternal protective factors for orofacial clefts. Eur J Oral Sci. 2010;118:325-32 pubmed publisher
    ..Altogether, our study identified a novel gene, the nucleotide variants of which were be associated with a decreased risk of having a baby with NCL/P. ..
  52. Hu Y, Chen E, Mu Y, Li J, Chen R. BHMT gene polymorphisms as risk factors for cleft lip and cleft palate in a Chinese population. Biomed Environ Sci. 2011;24:89-93 pubmed publisher
    ..020, OR=2.10, 95% CI=1.11-3.95). Our study suggests that polymorphism rs3797546 in the BHMT gene may confer genetic risk of NSCL/P in a recessive manner. ..
  53. Tsuchiya H, da Costa K, Lee S, Renga B, Jaeschke H, Yang Z, et al. Interactions Between Nuclear Receptor SHP and FOXA1 Maintain Oscillatory Homocysteine Homeostasis in Mice. Gastroenterology. 2015;148:1012-1023.e14 pubmed publisher
    ..SHP inhibits the transcriptional activation of Bhmt and cystathionine γ-lyase by FOXA1. ..
  54. Lupu D, Orozco L, Wang Y, Cullen J, Pellegrini M, Zeisel S. Altered methylation of specific DNA loci in the liver of Bhmt-null mice results in repression of Iqgap2 and F2rl2 and is associated with development of preneoplastic foci. FASEB J. 2017;31:2090-2103 pubmed publisher
    ..M., Pellegrini, M., Zeisel, S. H. Altered methylation of specific DNA loci in the liver of Bhmt-null mice results in repression of Iqgap2 and F2rl2 and is associated with development of preneoplastic foci. ..
  55. Imbard A, Benoist J, Esse R, Gupta S, Lebon S, De Vriese A, et al. High homocysteine induces betaine depletion. Biosci Rep. 2015;35: pubmed publisher
    ..In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte. ..
  56. Martínez Vega R, Partearroyo T, Vallecillo N, Varela Moreiras G, Pajares M, Varela Nieto I. Long-term omega-3 fatty acid supplementation prevents expression changes in cochlear homocysteine metabolism and ameliorates progressive hearing loss in C57BL/6J mice. J Nutr Biochem. 2015;26:1424-33 pubmed publisher
    ..Altogether, the results obtained suggest a long-term protective role of omega-3 supplementation on cochlear metabolism and progression of hearing loss. ..
  57. Marini N, Yang W, Asrani K, Witte J, Rine J, Lammer E, et al. Sequence variation in folate pathway genes and risks of human cleft lip with or without cleft palate. Am J Med Genet A. 2016;170:2777-2787 pubmed publisher
    ..8, 95%CI?=?1.2-6.3). This comprehensive study provides further direction on candidate loci to help disentangle the folate-related developmental phenomena in human clefting risk. © 2016 Wiley Periodicals, Inc. ..
  58. Moruzzi S, Udali S, Ruzzenente A, Guglielmi A, Guarini P, Martinelli N, et al. The RFC1 80G>A, among Common One-Carbon Polymorphisms, Relates to Survival Rate According to DNA Global Methylation in Primary Liver Cancers. PLoS ONE. 2016;11:e0167534 pubmed publisher
  59. Jacometo C, Zhou Z, Luchini D, Corrêa M, Loor J. Maternal supplementation with rumen-protected methionine increases prepartal plasma methionine concentration and alters hepatic mRNA abundance of 1-carbon, methionine, and transsulfuration pathways in neonatal Holstein calves. J Dairy Sci. 2017;100:3209-3219 pubmed publisher
    ..Whether the effects in MET calves were directly related to increased Met supply in utero remains to be determined. ..
  60. Riberio D, Cella P, da Silva L, Jordao A, Deminice R. Acute exercise alters homocysteine plasma concentration in an intensity-dependent manner due increased methyl flux in liver of rats. Life Sci. 2018;196:63-68 pubmed publisher
    ..Also, Hcy remethylation and transsulfuration are coordinately regulated to maintain methyl balance. ..
  61. Xu X, Gammon M, Zeisel S, Lee Y, Wetmur J, Teitelbaum S, et al. Choline metabolism and risk of breast cancer in a population-based study. FASEB J. 2008;22:2045-52 pubmed publisher
    ..We observed a significant interaction between dietary betaine intake and the PEMT rs7926 polymorphism (P(interaction)=0.04). Our findings suggest that choline metabolism may play an important role in breast cancer etiology. ..
  62. Nechiporuk V, Zaichko N, Korda М, Melnyk A, Koloshko O. SULPHUR-CONTAINING AMINO ACIDS METABOLISM IN EXPERIMENTAL HYPER- AND HYPOTHYROIDISM IN RATS. Georgian Med News. 2017;:96-102 pubmed
  63. Jurkowska H, Niewiadomski J, Hirschberger L, Roman H, Mazor K, Liu X, et al. Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo. Amino Acids. 2016;48:665-676 pubmed publisher
    ..Within the liver, mRNA abundance for both CSAD and BHMT was upregulated in parallel with protein levels, indicating regulation of BHMT and CSAD mRNA synthesis or degradation. ..
  64. Singhal N, Li S, Arning E, Alkhayer K, Clements R, Sarcyk Z, et al. Changes in Methionine Metabolism and Histone H3 Trimethylation Are Linked to Mitochondrial Defects in Multiple Sclerosis. J Neurosci. 2015;35:15170-86 pubmed publisher
    ..We also found expression of the enzyme betaine homocysteine methyltransferase in cortical neurons...
  65. Pérez Miguelsanz J, Vallecillo N, Garrido F, Reytor E, Perez Sala D, Pajares M. Betaine homocysteine S-methyltransferase emerges as a new player of the nuclear methionine cycle. Biochim Biophys Acta Mol Cell Res. 2017;1864:1165-1182 pubmed publisher
    ..Overall, our results support the involvement of BHMT in nuclear homocysteine remethylation, although moonlighting roles unrelated to its enzymatic activity in this compartment cannot be excluded. ..
  66. Sun K, Song J, Liu K, Fang K, Wang L, Wang X, et al. Associations between homocysteine metabolism related SNPs and carotid intima-media thickness: a Chinese sib pair study. J Thromb Thrombolysis. 2017;43:401-410 pubmed publisher
    ..007) and CIMT (p?=?0.022). Significant associations are found between Hcy metabolism related genetic polymorphisms, biochemical indexes and CIMT indexes. There are complex interactions between genetic polymorphisms for CCA-IMT and CIMT. ..
  67. Plohl O, Kralj S, Majaron B, Fröhlich E, Ponikvar Svet M, Makovec D, et al. Amphiphilic coatings for the protection of upconverting nanoparticles against dissolution in aqueous media. Dalton Trans. 2017;46:6975-6984 pubmed publisher
    ..However, only the PMAO-BHMT coating provided an effective protection against the dissolution of the UCNPs and long-term colloidal stability in PBS, and did not show cytotoxicity in EAhy926 endothelial cells. ..
  68. Misiak B, Łaczmański Ł, Słoka N, Szmida E, Piotrowski P, Loska O, et al. Metabolic dysregulation in first-episode schizophrenia patients with respect to genetic variation in one-carbon metabolism. Psychiatry Res. 2016;238:60-67 pubmed publisher
    ..None of them remained significant after Bonferroni correction. Our results indicate that metabolic dysregulation in patients with FES is not associated with genetic variation in one-carbon metabolism. ..
  69. Zeisel S. Choline, Other Methyl-Donors and Epigenetics. Nutrients. 2017;9: pubmed publisher
    ..Diet intake of choline can modulate methylation because, via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-..
  70. Omer N, Hu Y, Hu Y, Idriss A, Abobaker H, Hou Z, et al. Dietary betaine activates hepatic VTGII expression in laying hens associated with hypomethylation of GR gene promoter and enhanced GR expression. J Anim Sci Biotechnol. 2018;9:2 pubmed publisher
    ..Activation of hepatic VTGII expression may contribute, at least partly, to improved egg production in betaine-supplemented hens. ..
  71. Amorim M, Moura C, Gomes A, Barboza H, Lopes R, Ribeiro M, et al. Betaine-homocysteine methyltransferase 742G>A polymorphism and risk of down syndrome offspring in a Brazilian population. Mol Biol Rep. 2013;40:4685-9 pubmed publisher
    ..17; 95% CI: 0.04-0.80; P=0.01). Our results indicate that women harboring the single nucleotide polymorphism BHMT 742G>A have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect. ..
  72. Qin S, Zhou Y, Gray L, Kusebauch U, McEvoy L, Antoine D, et al. Identification of Organ-Enriched Protein Biomarkers of Acute Liver Injury by Targeted Quantitative Proteomics of Blood in Acetaminophen- and Carbon-Tetrachloride-Treated Mouse Models and Acetaminophen Overdose Patients. J Proteome Res. 2016;15:3724-3740 pubmed
    ..85, specificity: 0.84, accuracy: 85%). These five blood proteins are candidates for detecting acetaminophen-induced liver injury using next-generation diagnostic devices (e.g, microfluidic ELISA assays). ..
  73. Zhao N, Yang S, Hu Y, Dong H, Zhao R. Maternal betaine supplementation in rats induces intergenerational changes in hepatic IGF-1 expression and DNA methylation. Mol Nutr Food Res. 2017;61: pubmed publisher
    ..Concurrently, dietary betaine supplementation to F0 dams increased hepatic expression of betaine homocysteine methyltransferase, at both mRNA and protein levels, in F1, but not F2 pups...
  74. Xie W, Wood A, Lyssenko V, Weedon M, Knowles J, Alkayyali S, et al. Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes. Diabetes. 2013;62:2141-50 pubmed publisher
    ..Genetic variants associated with genes in the glycine biosynthesis pathways do not provide consistent evidence for a role of glycine in diabetes-related traits. ..
  75. Zhang Q, Bertics S, Luchini N, White H. The effect of increasing concentrations of dl-methionine and 2-hydroxy-4-(methylthio) butanoic acid on hepatic genes controlling methionine regeneration and gluconeogenesis. J Dairy Sci. 2016;99:8451-8460 pubmed publisher
    ..The lack of upregulation of gluconeogenesis indicates that increased dl-Met or HMB is not prioritized for glucose synthesis in primary bovine hepatocytes. ..
  76. Saha T, Chatterjee M, Verma D, Ray A, Sinha S, Rajamma U, et al. Genetic variants of the folate metabolic system and mild hyperhomocysteinemia may affect ADHD associated behavioral problems. Prog Neuropsychopharmacol Biol Psychiatry. 2018;84:1-10 pubmed publisher
    ..It can be inferred from the data obtained that folate system genetic variants and mild hyperhomocysteimenia may affect ADHD associated traits by attenuating folate metabolism. ..
  77. Xu X, Gammon M, Zeisel S, Bradshaw P, Wetmur J, Teitelbaum S, et al. High intakes of choline and betaine reduce breast cancer mortality in a population-based study. FASEB J. 2009;23:4022-8 pubmed publisher
    ..Our study supports the important roles of choline and betaine in breast carcinogenesis. It suggests that high intake of these nutrients may be a promising strategy to prevent the development of breast cancer and to reduce its mortality. ..
  78. Zhou Z, Garrow T, Dong X, Luchini D, Loor J. Hepatic Activity and Transcription of Betaine-Homocysteine Methyltransferase, Methionine Synthase, and Cystathionine Synthase in Periparturient Dairy Cows Are Altered to Different Extents by Supply of Methionine and Choline. J Nutr. 2017;147:11-19 pubmed publisher
    ..Failure to generate a comparable amount of endogenous Met from choline could be one reason that choline-fed cows fail to achieve comparable performance and health benefits during the periparturient period. ..
  79. Breksa A, Garrow T. Recombinant human liver betaine-homocysteine S-methyltransferase: identification of three cysteine residues critical for zinc binding. Biochemistry. 1999;38:13991-8 pubmed
    ..Some of the members of this family include the vitamin B(12)-dependent methionine synthases, E. coli S-methylmethionine-S-homocysteine methyltransferase, and A. bisulcatus S-methylmethionine-selenocysteine methyltransferase. ..
  80. Lapko V, Smith D, Smith J. S-methylated cysteines in human lens gamma S-crystallins. Biochemistry. 2002;41:14645-51 pubmed
    ..Evidence of more S-methylation in soluble than in insoluble gammaS-crystallins supports the contention that S-methylation of gammaS-crystallin inhibits protein insolubilization and may offer protection against cataract. ..
  81. Urzen J, Fullerton B. Nonsurgical Resolution of a Bucket Handle Meniscal Tear: A Case Report. PM R. 2016;8:1115-1118 pubmed publisher
    ..The patient reported resolution of pain with walking 8 months after the injury. Magnetic resonance imaging 10 months after the injury and arthroscopy 47 months after the injury showed complete resolution of the meniscal tear. V. ..
  82. Ahn C, Jun D, Na J, Choi Y, Kim Y. Alleviation of hepatic fat accumulation by betaine involves reduction of homocysteine via up-regulation of betaine-homocysteine methyltransferase (BHMT). Biochem Biophys Res Commun. 2016;477:440-7 pubmed publisher
    ..The results suggest that the beneficial effect of betaine against hepatic lipid accumulation may be attributed, at least in part, to the depletion of homocysteine via up-regulation of BHMT in hepatocytes. ..
  83. Colomina J, Cavallé Busquets P, Fernàndez Roig S, Solé Navais P, Fernandez Ballart J, Ballesteros M, et al. Maternal Folate Status and the BHMT c.716G>A Polymorphism Affect the Betaine Dimethylglycine Pathway during Pregnancy. Nutrients. 2016;8: pubmed
    ..11 [0.06], p = 0.055 to -0.23 [0.06], p < 0.001). During pregnancy, the BHMT pathway is affected by folate status and by the variant BHMT c.716A allele. ..
  84. Cao L, Wang Y, Zhang R, Dong L, Cui H, Fang Y, et al. Association of neural tube defects with gene polymorphisms in one-carbon metabolic pathway. Childs Nerv Syst. 2018;34:277-284 pubmed publisher
    ..It was confirmed that the gene variation related to OCM was one of the susceptibility factors for NTDs. ..
  85. Sunden S, Renduchintala M, Park E, Miklasz S, Garrow T. Betaine-homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene. Arch Biochem Biophys. 1997;345:171-4 pubmed
    ..Human liver and kidney were the only organs tested that expressed BHMT mRNA. Human pancreas, brain, heart, skeletal muscle, spleen, and placenta were devoid of BHMT mRNA. The human BHMT gene has been mapped to chromosome 5q13.1-q15. ..
  86. Hazra A, Fuchs C, Kawasaki T, Kirkner G, Hunter D, Ogino S. Germline polymorphisms in the one-carbon metabolism pathway and DNA methylation in colorectal cancer. Cancer Causes Control. 2010;21:331-45 pubmed publisher
    ..Collectively, these exploratory data provide suggestive evidence for the association of MTHFR 429 Ala/ Ala and TCN2 259 Arg/Arg and CIMP status in colorectal cancer. ..
  87. Ma H, Ning J, Jin X, Mao C, Bu X, Wang M, et al. Betaine homocysteine methyltransferase (BHMT) as a specific and sensitive blood marker for acute liver injury. Biomarkers. 2014;19:578-84 pubmed publisher
    ..However, the slopes of BHMT curves were steeper than ALT curves. And in three out of the five cases, BHMT levels peaked 1 day earlier than ALT levels be a sensitive marker with good prognostic value. ..
  88. Tang X, Cleves M, Nick T, Li M, MacLeod S, Erickson S, et al. Obstructive heart defects associated with candidate genes, maternal obesity, and folic acid supplementation. Am J Med Genet A. 2015;167:1231-42 pubmed publisher
  89. Ji C, Shinohara M, Vance D, Than T, Ookhtens M, Chan C, et al. Effect of transgenic extrahepatic expression of betaine-homocysteine methyltransferase on alcohol or homocysteine-induced fatty liver. Alcohol Clin Exp Res. 2008;32:1049-58 pubmed publisher
    ..Multiple mechanisms are involved in protection by betaine including increased SAM/SAH and PC/PE ratios. ..
  90. Goldmuntz E, Woyciechowski S, Renstrom D, Lupo P, Mitchell L. Variants of folate metabolism genes and the risk of conotruncal cardiac defects. Circ Cardiovasc Genet. 2008;1:126-32 pubmed publisher
  91. Giusti B, Saracini C, Bolli P, Magi A, Martinelli I, Peyvandi F, et al. Early-onset ischaemic stroke: analysis of 58 polymorphisms in 17 genes involved in methionine metabolism. Thromb Haemost. 2010;104:231-42 pubmed publisher
    ..This study identifies significant genetic associations between premature ischaemic stroke and haplotypes in BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS genes involved in methionine metabolism. ..
  92. Jin B, Gong Z, Yang N, Huang Z, Zeng S, Chen H, et al. Downregulation of betaine homocysteine methyltransferase (BHMT) in hepatocellular carcinoma associates with poor prognosis. Tumour Biol. 2016;37:5911-7 pubmed publisher
    b>Betaine homocysteine methyltransferase (BHMT) catalyzes the synthesis of methionine using betaine and homocysteine (Hcy), which is restricted to the liver and kidney...