Methylation : Neuropathy

Methylation is one of the most underappreciated, yet vital processes in human physiology. Among its many functions, methylation assists with DNA repair, it aids in removing unwanted toxins, helps maintain mood, and regulates inflammation. Chemically speaking, methylation refers to the addition of the molecule CH3, known as a methyl group, on a substrate. The use of CH3 in methylation occurs billions of times every second, and is utilized by the body for the proper function of virtually all body systems. Methylation should be viewed as a biochemical pathway, or “cycle” as it is commonly referred. At its core the methylation cycle serves to convert methionine, an essential amino acid, into homocysteine and back again. This is critical considering that homocysteine is a toxic amino acid implicated in a variety of degenerative conditions including diabetes, cervical dysplasia, colon cancer, lung cancer, osteoporosis, depression, cognitive dysfunction, neuropathies, and cardiovascular disease. It is important to understand that methionine converts into S-adenosyl methionine (SAM), which acts as a universal methyl donor. The formation of SAM is a critical event in cellular metabolism such that it serves as the source of methyl groups for all cellular processes involving methylation, and is the source of methyl groups involved in the epigenetic modulation of the genome.

Methylation is highly dependent upon good B vitamin status. In the image provided, one can see the recycling of homocysteine back to methionine, with intermediates SAM and S-Adenosylhomocysteine (SAH). When SAM methylates a molecule, it generates SAH and then homocysteine. In all cells, homocysteine can be converted back to methionine to begin the process anew with the help of B12 and folate. Further, vitamin B6 can rid the cell of extra homocysteine by converting it into cysteine, which in turn can be used to make glutathione, the primary cellular antioxidant. However, factors including illness, excessive toxin exposure, and genetic abnormalities can cause the process to malfunction, especially for those with a Single Nucleotide Polymorphism (SNP), or genetic variant, for MTHFR, the key enzyme in the methylation pathway which converts 5, 10 methylenetetrahydrofolate to 5-methyltetrahydrofolate, allowing for proper methylation. Given this context, one cannot overstate the importance of key B vitamins in their most bioavailable forms, specifically L-5-methyltetrahydrofolate (folate), methyl-cobalamin (B12), pyridoxal 5’-phosphate (B6), and riboflavin 5’-phosphate (B2).

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