COMT

COMT c.472

Inactivation of these neurotransmitters is important to ensure that the amount that binds to their receptors remain constant and at physiologically normal levels.
If these the COMT enzyme works to rapidly, or too slowly, behavioural changes can occur.

Heightened cognitive performance at the cost of greater levels of anxiety and vulnerability to stress
Significantly heightened startle reflex compared with the warriors 5, and gravitate toward harm avoidance, as opposed to the novelty seeking, as observed with the warrior genotype.
Two copies of the ‘A’ allele display lower COMT activity which is associated with increased dopamine levels in the brain. This is thought to lead to a lower pain threshold 6 and increased stress sensitivity 7 but improved memory and attention to detail 7, a potential risk for Parkinsons disease 8 has also been described. Carriers are therefore sometimes termed ‘Worriers’

Resilience to stress as well as an emotional advantage over individuals with the AG (worrier) genotype. Additionally, this genotype also confers protection against anxiety and pain susceptibility in these individuals
Two copies of the ‘G’ allele display higher COMT activity which is associated with decreased dopamine levels in the brain. This increased activity is thought to lead to a higher pain threshold 6 and capacity to deal with stress 7, at the expense of a reduction in cognitive performance in non-stressful environments. Therefore, carriers of two ‘G’ alleles are sometimes termed ‘Warriors

Dietary components that inhibit COMT activity include quercetin and tea catechins.
www.mygenefood.com/genes/brain-and-mental-health-genes/comt/

‘A’ allele, which is associated with low activity, is linked with increases in the potentially harmful homocysteine 10; often associated with an elevated cardiovascular risk 11. As the ‘A’ allele form of COMT displays reduced methylation activity its methyl donor source (methionine) builds up. Methionine is typically formed by the processing of homocysteine using either methionine synthase (MTR) or betaine homocysteine methyltransferase (BHMT). Typically methionine is rapidly used, however when it accumulates it blocks further MTR or BHMT activity leading to a homocysteine accumulation.

Magnesium is a cofactor for COMT, required for its efficient activity
Two copies of the ‘A’ allele of G472A, which is associated with a significant reduction in COMT activity may therefore benefit from magnesium supplementation.

no studies have directly assessed the impact on magnesium on those carrying two copies of the ‘A’ allele a general anti-depressive effect has been described 14.
magnesium is vital for a wide variety of functions it is not recommended for those carrying the ‘G’ allele to try and reduce magnesium intake.

Attaching a methyl group to a catechol substrate, including dopamine and catechol oestrogens, using S-adenosyl methionine (SAMe) as the methyl donor. The A allele leads to a 3 to 4 fold reduced activity of the enzyme and has been associated with an increased risk for certain cancers including breast and ovarian cancer. The GA and AA genotype has also been linked to decreased resilience to environmental stressors and thus an increased risk for anxiety related mood disorders.
COMT enzyme is also involved in methylating (and thereby inactivating)

This is the most active conjugation pathway for these catechol oestrogens, although they can also be conjugated by the process of glutathione conjugation and sulfation.
The enzyme is thus integral in health detoxification of oestrogen products.
COMT requires SAMe and magnesium as cofactors for this process of methylation.
dnalife.academy/comt/