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Glutamate-cysteine ligase catalytic subunit (GCLM) together with glutamate-cysteine ligase regulatory subunit (GCLC) forms an enzyme which is the first step in the cellular glutathione (GSH) biosynthetic pathway, and is encoded for by the GCLM gene.

Glutathione is an important antioxidant molecule which readily neutralizes reactive oxygen species, a major cause of oxidative stress, on other molecules 1, and is often thought of as the bodies first line of antioxidant defense. A simple molecule glutathione is formed from three amino acids cysteine, glycine and glutamate, with the first reaction (joining glutamate and cysteine) being catalyzed by the enzyme glutamate cysteine ligase (GCL). GCL is formed from two separate subunits GCLM and GCLC which regulate its function 2.

There is one SNP in GCLM that is linked with impaired health outcomes rs41303970.



Science Grade
rsID Number Major Allele Minor Allele Minor Allele Frequency (%)
rs41303970 c t 18

Risk Description

There is some evidence that the risk ‘T’ allele of C-590T in the GCLM gene is associated with impaired clearance of mercury which is a potent oxidant 3.

Mercury is typically eliminated from the body by antioxidants such as glutathione. However, in those carrying the risk ‘T’ allele, with an increased effect seen for those carrying two copies, increased retention of mercury was detected.

The authors of the study hypothesize that this is due to reduced glutathione synthesis in the body however no data has yet been provided to demonstrate this.

Lifestyle Considerations:

Behavior Description
Avoid mercury containing foods

Mercury is a well known toxin and so should be largely absent from the food chain.

Unfortunately due to increasing environmental pollution and the relative persistence of mercury in plants and animals it is known to bio-accumulate rapidly. Therefore those carrying the risk ‘T’ allele of C-590T may wish to avoid foods in which bio-magnification of mercury levels has occurred, such as certain fish and other apex predators 4.

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


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