AHCY

Protein:

Adenosylhomocysteinase


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Adenosylhomocysteinase is an enzyme that converts S-adenosylhomocysteine to homocysteine and adenosine and is encoded for by the AHCY gene 1.

AHCY is of interest due to its position in the methionine cycle, part of the wider methylation pathway. A major function of the methionine cycle is to produce S-adenosylmethionine (SAM-e). SAM-e is a major methyl donor required for more than 40 different reactions throughout the body ranging from control of  DNA methylation to the breakdown of lipids 2.

SAM-e deficiency has been linked with a variety of disorders including depression 3, arthritis 4 and fibromylagia 5, with supplementation improving symptoms although the mechanisms of its action are unclear. There are several SNPs found in the AHCY gene with three commonly discussed in other reports G274A or rs41301825, C112T or rs13043752 and A274G or rs41312290, although the latter has not been shown to have any impact on AHCY activity.

G274A, G123A

Science Score
Gastrointestinal Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs41301825 g a 0.8GlyArg

Risk Description

The rare risk allele ‘A’ of G274A in the AHCY gene is associated with reduced AHCY enzyme activity 6. However, although enzyme activity is reduced there have been no described associations with poor health outcomes. Additionally it is not clear how reduced enzyme activity will impact on the methionine cycle and wider methylation pathway. Based on its position in the pathway it is possible to hypothesize that homocysteine levels may be reduced but that SAM-e production may be inhibited by the buildup of S-adenosylhomocysteine.

Additionally during the conversion of S-adenosylhomocysteine to homocysteine an adenosine molecule is produced, which as we’ve discussed is vital for promoting healthy sleep. It is therefore possible to hypothesize that the risk ‘A’ allele may also interfere with sleep, although this has not been demonstrated in any system.

Indirect Nutrients:*

IngredientActive IngredientEffect
S-adenyosylmethionine (SAM-e)

The reduction in AHCY activity associated with the risk allele ‘A’ of G274A may lead to a build up of S-adenosylhomocysteine inhibiting the production of SAM-e. Therefore SAM-e supplementation may be beneficial, although care should be taken to not oversaturate an already overloaded pathway as this may lead to further complications.

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

C112T, A38T

Science Score
Gastrointestinal Health
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs13043752 c t 0.6ArgTrp

Risk Description

The rare risk allele ‘T’ of C112T in the AHCY gene is associated with reduced AHCY enzyme activity 6. Similarly to G274A above there have been no negative health associations associated with the reduction in AHCY enzyme activity. As a similar effect on enzyme activity is observed we can make the same hypotheses, predicting that homocysteine and adenosine levels may be reduced but that SAM-e production may be inhibited by the buildup of S-adenosylhomocysteine.

Indirect Nutrients:*

IngredientActive IngredientEffect
S-adenyosylmethionine (SAM-e)

As above the reduction in AHCY activity associated with the risk allele ‘T’ of C112T may promote the accumulation of S-adenosylhomocysteine which can in turn inhibit production of SAM-e. Therefore supplementation with SAM-e may prove beneficial, although care should be taken with dosing to prevent over saturation of the methionine cycle.

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

A274G, I92V

Science Score
rsID Number Major Allele Minor Allele Minor Allele Frequency (%) Major Amino Acid Minor Amino Acid
rs41312290 a g 0.1IleVal

Risk Description

While the two previous SNPs are associated with reduced AHCY enzyme activity no such effect was reported for A274G or rs41312290, although it is commonly reported alongside, due to appearing in the same research paper 6.

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

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