title: Effects of betaine in a murine model of mild cystathionine-beta-synthase deficiency.
abstract: Cystathionine-beta-synthase (CBS) is required for transsulfuration of homocysteine, an amino acid implicated in vascular disease. We studied homocysteine metabolism in mice with mild hyperhomocysteinemia due to a heterozygous disruption of the Cbs gene. Mice were fed diets supplemented with betaine or dimethylsulfonioacetate (DMSA); betaine and DMSA provide methyl groups for an alternate pathway of homocysteine metabolism, remethylation by betaine:homocysteine methyltransferase (BHMT). On control diets, heterozygous mice had 50% higher plasma homocysteine than did wild-type mice. Betaine and DMSA had similar effects in both genotype groups: liver betaine increased dramatically, while plasma homocysteine decreased by 40% to 50%. With increasing betaine supplementation, homocysteine decreased by 75%. Plasma homocysteine and BHMT activity both showed a strong negative correlation with liver betaine. Homocysteinemia in mice is sensitive to a disruption of Cbs and to methyl donor intake. Because betaine leads to a greater flux through BHMT and lowers homocysteine, betaine supplementation may be beneficial in mild hyperhomocysteinemia.
authors.affiliation: Department of Pediatrics, Montreal Children's Hospital, McGill University Health Center, Montrreal, Quebec, Canada.
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Schwahn
authors.forename: Udo
authors.initials: U
authors.lastname: Wendel
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lussier-Cacan
authors.forename: Mei-Heng
authors.initials: MH
authors.lastname: Mar
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
authors.forename: Daniel
authors.initials: D
authors.lastname: Leclerc
authors.forename: Carmen
authors.initials: C
authors.lastname: Castro
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Garrow
authors.forename: Rima
authors.initials: R
authors.lastname: Rozen
mesh_terms: D000821:Animal Feed; D000818:Animals; D001622:Betaine / Q000378:metabolism / Q000494:pharmacology*; D050940:Betaine-Homocysteine S-Methyltransferase; D002794:Choline / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000172:deficiency* / Q000235:genetics; D003545:Cysteine / Q000097:blood; D005260:Female; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008082:Lipotropic Agents / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000097:blood; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012044:Regression Analysis; D012694:Serine / Q000097:blood
chemical_list: D008082:Lipotropic Agents; D006710:Homocysteine; D001622:Betaine; D012694:Serine; D008715:Methionine; D008780:Methyltransferases; D050940:Betaine-Homocysteine S-Methyltransferase; C494549:Bhmt protein, mouse; D003541:Cystathionine beta-Synthase; D003545:Cysteine; D002794:Choline