Betaine-homocysteine methyltransferase-2: cDNA cloning, gene sequence, physical mapping, and expression of the human and mouse genes.

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.