BHMT

BHMT stands for betaine-homocysteine S-methyltransferase, a cytosolic enzyme that remethylates homocysteine to methionine using betaine as the methyl donor. The reaction converts homocysteine and betaine into methionine and dimethylglycine, thereby contributing to the methionine cycle.

In humans, BHMT is primarily expressed in the liver and to a lesser extent in the kidney. The enzyme is encoded by the BHMT gene. It is a zinc-dependent methyltransferase that operates in a folate-independent remethylation pathway, complementing the activity of methionine synthase, which uses 5-m methyl-tetrahydrofolate and vitamin B12.

BHMT relies on betaine, derived from choline oxidation, as the methyl donor instead of S-adenosylmethionine. This pathway helps maintain methionine and S-adenosylmethionine pools, especially when folate- or B12-dependent remethylation is limited, and it contributes to the regulation of homocysteine levels.

Clinical and metabolic relevance of BHMT arises from its influence on homocysteine metabolism. Variations in BHMT activity or expression can affect plasma homocysteine and methionine concentrations, and have been investigated for associations with cardiovascular risk and other conditions. Dietary intake of betaine and choline can modulate the flux through the BHMT pathway, linking nutrition to methionine metabolism and homocysteine homeostasis. Overall, BHMT is a key component of the methylation system, operating in a parallel route to folate-dependent remethylation to sustain essential methyl group transfers.