BHMT (betaine-homocysteine methyltransferase)
The liver enzyme that recycles homocysteine using betaine as the methyl donor
Definition
BHMT (betaine-homocysteine methyltransferase) is a zinc-dependent enzyme, highly abundant in the liver, that converts homocysteine back into methionine by transferring a methyl group from betaine (trimethylglycine). It is one of the two homocysteine remethylation routes —the other depends on folate and vitamin B12— and handles roughly 25% of the liver's homocysteine turnover. By replenishing methionine, BHMT feeds the synthesis of S-adenosylmethionine (SAMe), the universal methyl donor for hundreds of cellular reactions. Its activity is central to keeping homocysteine within safe levels and to sustaining the body's methylation capacity.
Detailed explanation
BHMT accounts for 0.6–1% of total liver protein, reflecting its central role in one-carbon metabolism. It catalyses the transfer of a methyl group from betaine to homocysteine, producing methionine and dimethylglycine. Methionine is then activated to SAMe, whose ratio to SAH (the SAMe/SAH ratio) sets the organism's methylation capacity —relevant to DNA methylation and therefore to epigenetic age.
A complementary route exists: folate/B12-dependent remethylation via methionine synthase. When that route falters —through B12 or folate deficiency or MTHFR polymorphisms (C677T)— the BHMT-betaine pathway becomes an important rescue route to lower homocysteine. This is why supplementing betaine/trimethylglycine (TMG) reduces hyperhomocysteinemia even when the underlying problem lies in the folate cycle.
Common genetic variants in the BHMT gene modulate its activity and plasma homocysteine levels. A homologous enzyme, BHMT-2, uses S-methylmethionine rather than betaine as its methyl donor. BHMT requires zinc in its active site and depends on specific potassium-ion interactions to bind homocysteine efficiently.
Scientific sources
- PubMed — Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism?
- PubMed — Human betaine-homocysteine methyltransferase (BHMT) and BHMT2: common gene sequence variation and functional characterization
- PubMed — Betaine-homocysteine S-methyltransferase-2 is an S-methylmethionine-homocysteine methyltransferase
- PubMed — Specific potassium ion interactions facilitate homocysteine binding to betaine-homocysteine S-methyltransferase
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