Effects of betaine in a murine model of mild cystathionine-β-synthase deficiency

Cystathionine-β-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...

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Veröffentlicht in:Metabolism, clinical and experimental clinical and experimental, 2004-05, Vol.53 (5), p.594-599
Hauptverfasser: Schwahn, Bernd C, Wendel, Udo, Lussier-Cacan, Suzanne, Mar, Mei-Heng, Zeisel, Steven H, Leclerc, Daniel, Castro, Carmen, Garrow, Timothy A, Rozen, Rima
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container_end_page 599
container_issue 5
container_start_page 594
container_title Metabolism, clinical and experimental
container_volume 53
creator Schwahn, Bernd C
Wendel, Udo
Lussier-Cacan, Suzanne
Mar, Mei-Heng
Zeisel, Steven H
Leclerc, Daniel
Castro, Carmen
Garrow, Timothy A
Rozen, Rima
description Cystathionine-β-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.
doi_str_mv 10.1016/j.metabol.2003.10.033
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subjects Animal Feed
Animals
Betaine - metabolism
Betaine - pharmacology
Betaine-Homocysteine S-Methyltransferase
Biological and medical sciences
Choline - metabolism
Cystathionine beta-Synthase - deficiency
Cystathionine beta-Synthase - genetics
Cysteine - blood
Female
Heterozygote
Homocysteine - blood
Homocysteine - metabolism
Hyperhomocysteinemia - drug therapy
Hyperhomocysteinemia - genetics
Hyperhomocysteinemia - metabolism
Lipotropic Agents - metabolism
Lipotropic Agents - pharmacology
Liver - metabolism
Male
Medical sciences
Metabolic diseases
Metals (hemochromatosis...)
Methionine - blood
Methyltransferases - metabolism
Mice
Mice, Inbred C57BL
Other metabolic disorders
Regression Analysis
Serine - blood
title Effects of betaine in a murine model of mild cystathionine-β-synthase deficiency
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