ArticleThe Journal of biological chemistry2011
Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and 1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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Who cites it
125 citing papers in PubMed, 215 citations in OpenAlex.
- Ischemic Stroke Increases Protein Expression of the Folate Receptor and One-carbon Enzymes in Brain Tissue From Male and Female Patients.Translational stroke research · 2026Article
- Complementary hyperpolarizedNpj imaging · 2026Article
- Lowered Maternal and Paternal Plasma Concentrations of Choline Are Associated with the Severity of Congenital Heart Defects in the Offspring.Nutrients · 2026Article
- Hepatocyte-Specific Deletion of Betaine-Homocysteine Methyltransferase Disrupts Methionine Metabolism and Promotes the Spontaneous Development of Hepatic Steatosis.Biomolecules · 2026Article
- Methionine and choline deficiency rewires transcriptional programs to recapitulate molecular features of human MASH.Journal of lipid research · 2026Article
- PPARγ-dependent and -independent regulation of methionine metabolism by diet-induced obesity and fasting in male mice.bioRxiv : the preprint server for biology · 2026Article
- Paradoxical oncogenic effects of hepatic Brca1 through modulating Bhmt.Scientific reports · 2026Article
- PPARγ-dependent and -independent regulation of genes involved in hepatic methionine cycle in fasted or diet-induced obese mice.PloS one · 2026Article
- Role of hyperhomocysteinemia in atherosclerosis: from bench to bedside.Annals of medicine · 2025Review
- AMPK-Dependent Epigenetic Regulation of Metabolism Mediates the Anti-Cancer Action of Pterostilbene in Hepatocellular Carcinoma.Molecular nutrition & food research · 2025Article
- Review
- Identification and validation of key target genes of penning formula for treating rat chronic endometritis model.Scientific reports · 2025Article
- LncRNA H19 promoted alcohol-associated liver disease through dysregulation of alternative splicing and methionine metabolism.Hepatology (Baltimore, Md.) · 2025Article
- Identification of methionine metabolism related prognostic model and tumor suppressive functions of BHMT in hepatocellular carcinoma.Scientific reports · 2025Article
- Eggs, Dietary Choline, and Nonalcoholic Fatty Liver Disease in the Framingham Heart Study.The Journal of nutrition · 2025Article
- One carbon metabolism supplementation in maturation medium but not embryo culture medium improves the yield of blastocysts from bovine oocytes.Scientific reports · 2025Article
- Common genetic polymorphisms define one-carbon metabolite responses to different forms of choline in healthy adult males.Frontiers in nutrition · 2025Article
- Chemogenomic Screening in a Patient-Derived 3D Fatty Liver Disease Model Reveals the CHRM1-TRPM8 Axis as a Novel Module for Targeted Intervention.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Metabolomics at the cutting edge of risk prediction of MASLD.Cell reports. Medicine · 2024Review
- The rate of muscle wasting in liver transplant recipients on waiting list: post-transplant outcomes and associated serum metabolite patterns.Hepatobiliary surgery and nutrition · 2024Article
65 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Betaine-homocysteine S-methyltransferase (BHMT) uses betaine to catalyze the conversion of homocysteine (Hcy) to methionine. There are common genetic polymorphisms in the BHMT gene in humans that can alter its enzymatic activity. We generated the first Bhmt(-/-) mouse to model the functional effects of mutations that result in reduced BHMT activity. Deletion of Bhmt resulted in a 6-fold increase (p < 0.01) in hepatic and an 8-fold increase (p < 0.01) in plasma total Hcy concentrations. Deletion of Bhmt resulted in a 43% reduction in hepatic S-adenosylmethionine (AdoMet) (p < 0.01) and a 3-fold increase in hepatic S-adenosylhomocysteine (AdoHcy) (p < 0.01) concentrations, resulting in a 75% reduction in methylation potential (AdoMet:AdoHcy) (p < 0.01). Bhmt(-/-) mice accumulated betaine in most tissues, including a 21-fold increase in the liver concentration compared with wild type (WT) (p < 0.01). These mice had lower concentrations of choline, phosphocholine, glycerophosphocholine, phosphatidylcholine, and sphingomyelin in several tissues. At 5 weeks of age, Bhmt(-/-) mice had 36% lower total hepatic phospholipid concentrations and a 6-fold increase in hepatic triacyglycerol concentrations compared with WT (p < 0.01), which was due to a decrease in the secretion of very low density lipoproteins. At 1 year of age, 64% of Bhmt(-/-) mice had visible hepatic tumors. Histopathological analysis revealed that Bhmt(-/-) mice developed hepatocellular carcinoma or carcinoma precursors. These results indicate that BHMT has an important role in Hcy, choline, and one-carbon homeostasis. A lack of Bhmt also affects susceptibility to fatty liver and hepatocellular carcinoma. We suggest that functional polymorphisms in BHMT that significantly reduce activity may have similar effects in humans.
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