Effects of betaine in a murine model of mild cystathionine-beta-synthase deficiency.
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.
Schwahn
Bernd C
BC
Department of Pediatrics, Montreal Children's Hospital, McGill University Health Center, Montrreal, Quebec, Canada.
Wendel
Udo
U
Lussier-Cacan
Suzanne
S
Mar
Mei-Heng
MH
Zeisel
Steven H
SH
Leclerc
Daniel
D
Castro
Carmen
C
Garrow
Timothy A
TA
Rozen
Rima
R
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
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