BHMT

Protein:

Betaine-Homocysteine S-Methyltransferase

SNP ID:

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Betaine-Homocysteine S-Methyltransferase (BHMT) is an enzyme that converts homocysteine into methionine, and is encoded for by the BHMT gene. BHMT functions by replacing a hydrogen atom on homocysteine with a methyl group donated by a betaine molecule (typically trimethylglycine). This activity is normal and is one of two methods, along with methionine synthase, used to provide the body with the essential amino acid methionine 1.

BHMT is of interest due to its capacity to bypass issues with the wider methylation cycle comprised of the methionine cycle and one carbon pathway, in which methionine synthase plays a major role. There are several SNPs located in the methylenetetrahydrofolate reductase (MTHFR) gene which limit its function, which in turn lead to a shortage of 5-methlytetrahydrofolate (MTHF). MTHF is required by methionine synthase to convert the harmful homocysteine into methionine, keeping the one carbon pathway turning thus preventing an accumulation of folate.

In people carrying SNPs which impair MTHFR function, homocysteine can build up to harmful levels, and reduced levels of methionine can also impact health. Therefore, the ability of BHMT to also convert homocysteine into methionine, independently of MTHFR function is of great interest.

There is one SNP in the BHMT gene which is associated with poor health outcomes, rs3733890 or  G716A.

G716A

Science Score
Gastrointestinal Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
 rs3733890 g a 30ArgGln

Risk Description

It is unclear which allele, if either of G716A presents a risk.

The ‘A’ allele of G716A is associated with increased homocysteine levels in the blood 2. Elevated homocysteine can be very damaging to tissue, particularly the specialized endothelial tissue which lines the blood vessels and heart. As such it is typically associated with increased cardiovascular risks 3.

Interestingly the ‘A’ allele of G716A which was associated with elevated homocysteine was actually protective against coronary artery disease 4; although in this study no difference in homocysteine levels was observed.

One potential explanation for this discrepancy is that the decreased cardiovascular risk may be due to BHMTs secondary role in fat metabolism, rather than its direct involvement in homocysteine metabolism. Betaine, the methyl donor used by BHMT in the conversion of homocysteine to methionine is derived from choline. As choline is also required for for the formation of lipoproteins it is possible that the ‘A’ allele of BHMT leads to greater betaine usage, depleting choline and thus limiting lipoprotein formation 5.

Direct Nutrients:*

IngredientActive IngredientEffect
Betaine Trimethylglycine

Betaine serves as a methyl donor in the conversion of the harmful homocysteine into the essential acid methionine by BHMT 6.

As it is unclear whether the ‘G’ or ‘A’ allele of G716A presents a risk supplementation with betaine may only be required if other deficiencies in homocysteine clearance are present.

Indirect Nutrients:*

IngredientActive IngredientEffect
Choline

Betaine which is required for BHMT function can be derived from choline 7.

It is not clear whether the ‘G’ or ‘A’ allele of G716A presents a risk, therefore choline supplementation to reduce homocysteine accumulation may only be required if other deficiencies are present.

Discuss this information with your doctor before taking any course of action.

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