What is MTHFR?

Humans have about 20,000 genes, among those is the MTHFR gene. According to the Genetics Home Reference the MTHFR gene provides instructions for making an enzyme called Methylenetetrahydrofolate Reductase. This enzyme plays a role in processing amino acids, the building blocks of proteins. Methylenetetrahydrofolate Reductase is important for a chemical reaction involving forms of the vitamin folate (also called vitamin B9)9. When eating food that contains folic acid, MTHFR converts it into methyl-folate, folates active form. Loss of this important step is crucial as methyl-folate plays a role in just about everything in the body. Methyl-folate plays a key role in methylation, the process of adding a methyl group to a compound 11. Methylation is involved in controlling homocysteine, a sulfur-containing amino acid that can affect plasma levels. B-vitamins folate, vitamin B12 and vitamin B6 are required for homocysteine (Hcy) metabolism; suboptimal folate status, together with the other B-vitamins deficiency, is commonly related to elevated plasma Hcy, as a consequence of the role that folate plays in the one-carbon metabolism 13.

MTHFR not only plays a vital role in the metabolism of folate but also DNA methylation, and RNA synthesis by catalyzing and conversion of 5, 10 MTHFR to 5 MTHF, a valuable enzyme in metabolizing folate and regulation of one carbon unit proportionally between methylation reaction and the synthesis of nucleic acid 3. This reaction is required for the multi-step process that converts the amino acid homocysteine into another amino acid, methionine. The body uses methionine to make proteins and other important compounds 9. MTHFR is the active metabolite of folate, 5-MTHF is involved in homocysteine remethylation creating methionine at a reduced rate 2. 5-MTHF can cross the barrier between blood and the brain required substrate for remethylation of homocysteine to methionine during methionine synthesis. A deficiency of MTHFR enzyme results in low methionine and hence a reduction in S-adenosylmethionine (SAMe), with elevated homocysteine levels. The pathology of the MTHFR deficiency is not fully understood, SAMe an important methyl donor, is needed for maintenance and formation of myelin in the brain. Therefore, a defect in methylation is likely to contribute to neurological problems. The higher levels of homocysteine can also result in an increased risk of thrombosis 7. Ferlazzo et al.'s (2017) claim folate is a source of DNA methylation, the addition of one methyl group is an important epigenetic modification where cytosine proceeds guanine, called CpG dinucleotides is critical in normal regulation and development of the genome 4.

Find out more by viewing the sub-pages of the MTHFR Gene.