MTR Gene.
Methionine Synthase
The enzyme that recycles homocysteine back to methionine using B12 and folate.
What MTR does.
MTR (methionine synthase) is the main enzyme that converts homocysteine back to methionine—completing the methylation cycle.
The reaction:
Homocysteine + Methylfolate → Methionine + THF
(Requires methylcobalamin/B12 as cofactor)
Why it matters
- • Keeps homocysteine from accumulating
- • Regenerates methionine for SAMe production
- • Connects folate and B12 metabolism
- • Essential for DNA synthesis and repair
When it's impaired
- • Homocysteine rises
- • Methionine and SAMe decrease
- • Folate gets 'trapped' as methylfolate
- • B12 deficiency symptoms appear
Common variants.
A2756G (rs1805087)
Most studied variantThe G allele may increase enzyme activity but also increase B12 requirements. Mixed research results.
Frequency: G allele: ~15-25% in most populations
Research note
MTR variants are less studied than MTHFR. The clinical significance of most variants is unclear. B12 status likely matters more than the gene variant itself.
The B12 connection.
MTR absolutely requires methylcobalamin (B12) to function. This is why B12 deficiency mimics folate deficiency—folate gets 'trapped' when MTR can't work.
Cofactors for MTR:
MTR vs BHMT: Two paths to methionine.
The body has two ways to recycle homocysteine to methionine. When one pathway is compromised, the other can compensate.
MTR pathway
- • Uses methylfolate + B12
- • Active in all tissues
- • Primary pathway for most of the body
- • Connects to MTHFR upstream
BHMT pathway
- • Uses betaine (TMG)
- • Mainly in liver and kidneys
- • Backup pathway
- • Can compensate for MTR issues
"This is why betaine (TMG) can help when B12 or folate pathways are compromised."
Genes don't act alone.
MTR doesn't determine your fate. It reveals where the system might need support.
Where it matters
MTR is expressed in all tissues but is especially important in rapidly dividing cells and the nervous system.
Expression depends on
- • Nutrient availability
- • Sunlight exposure
- • Toxin burden
- • Cell turnover rate
- • Age and hormonal status
SNPs are throttles, not defects
Genetic variants often slow down pathways to protect the system from overwhelm. They reveal where you need to go slower, not that you're broken.
The real question
Not "what does this gene do?" but "what is this pathway already struggling with that makes this gene relevant?"
Related patterns
"Genes don't cause outcomes. They reveal where the system is already under pressure."
Support strategies.
Ensure adequate B12
Methylcobalamin or adenosylcobalamin are the active forms. Check serum B12 AND methylmalonic acid (MMA) for true status.
Support with methylfolate
MTR uses methylfolate as the methyl donor. Methylfolate (5-MTHF) is the active form.
Consider betaine (TMG)
Supports the BHMT backup pathway. Helpful when MTR function is compromised.
Monitor homocysteine
Rising homocysteine indicates the cycle isn't working well. Target <8 μmol/L.
MTR connects folate and B12.
Without adequate B12, the best folate in the world won't help. MTR is where these two nutrients meet.