Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anomalies in folate and homocysteine metabolism can result in homocysteinemia and are implicated in disorders ranging from vascular disease to neural tube defects. Two enzymes are known to methylate homocysteine, vitamin B(12)-dependent methionine synthase (MTR) and betaine-homocysteine methyltransferase (BHMT). BHMT uses betaine, an intermediate of choline oxidation, as a methyl donor and is expressed primarily in the liver and kidney. We report the discovery of a novel betaine-homocysteine methyltransferase gene in humans and mice. The human BHMT2 gene is predicted to encode a 363-amino-acid protein (40.3 kDa) that shows 73% amino acid identity to BHMT. The BHMT2 transcript in humans is most abundant in adult liver and kidney and is found at reduced levels in the brain, heart, and skeletal muscle. The mouse Bhmt2 gene shows 69% amino acid identity and 79% similarity to the mouse Bhmt gene and 82% amino acid identity and 87% similarity to the human BHMT2 gene. Bhmt2 is expressed in fetal heart, lung, liver, kidney and eye. The discovery of a third gene with putative homocysteine methyltransferase activity is important for understanding the biochemical balance in using methyltetrahydrofolate and betaine as methyl donors as well as the metabolic flux between folate and choline metabolism in health and disease.
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PMID:Betaine-homocysteine methyltransferase-2: cDNA cloning, gene sequence, physical mapping, and expression of the human and mouse genes. 1108 63

Total plasma homocysteine (Hcy) concentration correlates with risk of vascular disease. Over 80% of chronic renal failure patients have elevated plasma Hcy and a 10-20 times higher incidence of vascular disease. Glycine betaine lowers plasma Hcy through methylation catalysed by betaine-homocysteine methyltransferase (BHMT). Dimethylthetin (DMT), a synthetic glycine betaine analogue, is a more effective BHMT substrate. DMT is therefore a potential therapeutic agent for reducing plasma Hcy in humans and may be particularly useful in renal failure patients receiving dialysis because of chronic betaine depletion as a result of treatment. We aimed to determine whether the addition of DMT to dialysis fluid lowered plasma Hcy concentrations in a Continuous Ambulatory Peritoneal Dialysis sheep model using animals that were either in acute renal failure (n=3) or had normal renal function (n=1). Sub-acute exposure to DMT was toxic to all four animals, which died with total lung consolidation and collapse and Diffuse Alveolar Damage within 48 h of beginning treatment. Adverse side effects were observed after 4-8 doses. DMT was not detected in pre-dialysis plasma samples and the final concentration at death was 0.5-7.8 mmol/L, depending on the number of doses each animal was exposed to. Abnormalities were not observed in animals supplied standard dialysis fluid, or fluid with added glycine betaine. Toxicity associated with DMT treatment raises concerns for its use in further studies. However, sub-acute administration of DMT to sheep may provide a useful model of acute alveolar damage.
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PMID:Dimethylthetin treatment causes diffuse alveolar lung damage: a pilot study in a sheep model of Continuous Ambulatory Peritoneal Dialysis (CAPD). 1717 48