Vitamin paradox in obesity: Deficiency or excess?

Figure 1 Relationship between methyl donors and mediators in the methylation of substrates. Methylation is a methyl-group transfer reaction from a methyl donor to a substrate, which is mediated by the methionine (Met) cycle. The deep red-arrow lines indicate the flow/transfer of methyl groups/one-carbon units from dietary sources to substrates. In this regard, methylation can be considered as a reaction between betaine and substrates (dashed line). An increase in the levels of substrates will increase the demand for betaine rather than for methylation mediators, e.g., folate and vitamin B₁₂ (B₁₂), because betaine is a non-renewable resource, while the mediators can be recycled if there is an adequate supply of methyl donors. Pathway 1: Betaine-dependent homocysteine (Hcy) remethylation; Pathway 2: Folate-dependent Hcy remethylation. BHMT: Betaine-homocysteine-methyltransferase; CAs: Catecholamines; CH₂-THF: 5,10-methylene tetrahydrofolate; CH3: Methyl groups; MeFox: An oxidation product of 5-methyltetrahydrofolate; MS: Methionine synthase; MTs: Methyltransferases; SAH: S-adenosylhomocysteine; SAM: S-adenosylmethionine; THF: Tetrahydrofolate.