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Methionine synthase (MS) is an enzyme encoded for by the MTR gene 1. MS is a key enzyme in the methionine cycle, which forms part of the wider methylation pathway. MS generates methionine from homocysteine using 5-MTHF as a donor for a methyl group. With a lack of  5-MTHF, as occurs in those with less functional MTHFR, this reaction stalls and leads to an accumulation of homocysteine.

There is also one SNP of interested associated with altered MS activity.


Science Grade
Endocrine Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs1805087 a g 20 Asp Gly

Risk Description

The SNP rs1805087 in the MTR gene is interesting as both the A and G alleles may are associated with different risks. From the angle of elevated homocysteine levels the major ‘A’ allele is actually the risk allele as it is associated with a reduced activity and therefore potentially the buildup of homocysteine, especially when present in association with other mutations in methylation cycle enzymes (MTHFR, MTRR, SHMT1)2.

However, as the minor ‘G’ allele is associated with increased MS activity it has also been associated with increased levels of DNA methylation3. This process is fundamental to life, but dysregulation has been linked with a host of other disorders, however, the exact impact of the ‘G’ allele of rs1805087 in these conditions remains unknown.


Direct Nutrients:*

Ingredient Active Ingredient Effect
Vitamin B12 Methylcobalamin

Vitamin B12 is a cofactor for MS 4. When bound MS can process homocysteine into the essential amino acid methionine.

The ‘A’ allele of rs1805087 in the MTR gene is associated with decreased MS activity and as such supplementing with vitamin B12 may prove beneficial, although there are currently no studies detailing dosage rates.

Conversely, the ‘G’ allele is associated with an increased activity. Where vitamin B12 is abundant then there should be no direct issue with the ‘G’ allele. However, in a diet lacking vitamin B12 it may be used up more quickly, limiting MS and other enzyme activity. As such it is unclear what advice to offer those with the ‘G’ allele.



Zinc is required for the processing of homocysteine into methionine by the enzyme MS 5. Zinc binds to homocysteine and primes it allowing the reaction to proceed, therefore those with the ‘A’ allele of rs1805087 (which is associated with reduced MS activity and higher levels of homocysteine2) may benefit from zinc supplementation in order to ensure maximal MS activity.

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


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