MTHFR (Methylenetetrahydrofoltate Reductase)
- MTHFR 677 C>T
- MTHFR 1298 A>C
Methylenetetrahydrofolate reductase is a riboflavin-dependent (FAD) enzyme that catalyses the NADPH-dependent reduction of 5,10-methylene-tetrahydrofolate (THF) to 5-methyl-THF.
It is a key enzyme in the folate metabolism pathway, directing folate from the diet either to DNA synthesis or homocysteine remethylation, a process by which homocysteine is converted back to Methionine.
The two polymorphisms described, occur at relatively high frequencies in the population, approximately 10-30%, and lower the activity of the MTHFR enzyme.
MTR (Methionine Synthase)
The methionine synthase (MS) enzyme, encoded by MTR, catalyses the remethylation of homocysteine to methionine. This reaction is vitamin B-12 dependent, and activity is essential to supply methionine for SAM synthesis and to prevent accumulation of homocysteine and SAH.
There is a common polymorphism which affects the functional site of the protein and hence the levels of circulating folate and homocysteine.
MTRR (Methionine Synthase Reductase)
Methionine Synthase Reductase is involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the maintenance of methionine synthase in a functional state.
It catalyses methylcobalamin, an essential cofactor of methionine synthase (MS), which is essential for maintaining adequate intracellular pools of methionine and is also responsible for maintaining homocysteine concentrations at non-toxic levels.
CBS (Cystathionine β Synthase)
CBS is a vitamin B6 dependent enzyme, which catalyses the irreversible conversion of homocysteine to cystathionine. It is directly involved in the removal of homocysteine from the methionine cycle, thus any alterations in its activity could affect homocysteine levels. Cystathionine is then converted to cysteine. Together with glutamate and glycine, glutathione can then be produced.
COMT catalyses the transfer of a methyl group from S-adenosylmethionine to catecholamines, including the neurotransmitters dopamine, epinephrine, and norepinephrine. This O-methylation results in one of the major degradative pathways of the catecholamine transmitters.
In addition to its role in the metabolism of endogenous substances, COMT is important in the metabolism of catechol drugs used in the treatment of hypertension, asthma and Parkinson disease.
Soluble catechol-O-methyltransferase (S-COMT) helps control the levels of certain hormones and is also involved in methylation and inactivation of catechol oestrogens. A genetic variant of the COMT gene reduces the activity of the enzyme and has been associated with breast and ovarian cancer; substance use disorder, and mental disorders such as schizophrenia, anxiety, bipolar and depression.
It may sound like something out of a sci-fi movie, but genetic testing is a powerful health tool that can give you a deep understanding of how your body works.
At the heart of it is the molecule DNA. Every single cell in our bodies – from our heart to skin, blood and bone – contains a complete set of our DNA. This powerful molecule carries our genetic code and determines all manner of traits, from our eye colour to aspects of our personalities and, of course, our health. Interestingly, 99.9% of the DNA from two people is identical. It’s the other 0.1% of DNA code sequences that make us unique.
An example of a genetic variation is that one ‘letter’ may be replaced by another. These variations can lead to changes in the resulting proteins being made. For example, a ‘C’ may be changed to a ‘G’ at a point in the genetic code. When the variation affects only one genetic ‘letter’ it is called a Single Nucleotide Polymorphism, or SNP (pronounced “snip”). Variations can however also affect more than one ‘letter’. Genetic tests look at specific chromosomes, genes or proteins, and the variations that occur within them, to make observations about disease or disease risk, body processes or physical traits.