BHMT-2 is highly homologous to Betaine-Homocysteine Methyltransferase (BHMT), but unlike BHMT, BHMT-2 cannot use betaine as a methyl donor . Instead, it specifically utilizes SMM, which is derived from plants and yeast . The enzyme is abundantly expressed in the liver and kidney, indicating its significant role in these organs .
The genes encoding BHMT and BHMT-2 are located adjacent to each other on human chromosome 5 (5q13), suggesting they are tandem duplicates . This proximity indicates a possible evolutionary relationship between the two enzymes. BHMT-2’s ability to use SMM instead of betaine might have evolved to provide an alternative pathway for homocysteine methylation in specific physiological conditions .
BHMT-2’s role in homocysteine metabolism makes it a potential target for therapeutic interventions aimed at reducing homocysteine levels in the blood. Elevated homocysteine levels are associated with an increased risk of cardiovascular diseases, making BHMT-2 a significant enzyme in medical research .
Several compounds have been tested as inhibitors of BHMT-2. Unlike BHMT, BHMT-2’s activity is not inhibited by dimethylglycine and betaine . Methionine is a stronger inhibitor of BHMT-2 compared to BHMT, and S-adenosylmethionine is a weak inhibitor of BHMT-2 . These differences in inhibitor sensitivity highlight the unique regulatory mechanisms of BHMT-2.