Do Methylation Pathways Carry Microbially Derived Deuterium-Depleted Methyl Groups to Support Mitochondrial Health?

One-carbon metabolism (also known as the methylation pathway) is a fundamental biochemical process involving the transfer of methyl groups from one molecule to another, to carry out many cellular functions, including DNA, RNA, and protein methylation and phosphatidylcholine synthesis. Many chronic diseases are linked to its dysfunction. The pathway centers on S-adenosylmethionine (SAMe), the universal methyl donor. The methyl group is sourced from methyl-tetrahydrofolate, and methionine, glycine, serine, and formaldehyde are carriers of one-carbon units. An overlooked aspect is the crucial role that the gut microbiome plays in assuring that the one-carbon units are virtually free of deuterium. Deuterium is a natural heavy isotope of hydrogen, and it damages the ATPase pumps in the mitochondria. Microbes produce extremely deuterium depleted (deupleted) hydrogen gas which they use as a reducing agent to convert carbon dioxide into organic molecules, such as acetate, butyrate and formate. We show here through an in-depth review of methylation and demethylation processes how they are used to deliver deupleted protons to the mitochondria, to protect them from damage. Toxic exposures to organophosphate insecticides and deficiencies in nutrients such as methionine, choline, betaine, and serine can impair methylation pathways, causing disease through co-causality of mitochondrial dysfunction.