Figure 2.

Cellular role of B12 in lipogenesis. There is a reduction in the production of methionine as well as the methyl donor s-adenosyl methionine (SAM) within the cell’s cytosol, resulting from B12 deficiency, leading to hyperhomocysteinemia as well as reversible increase in s-adenosyl homocysteine (SAH) which is known to be an inhibitor of DNA methyl transferases (DNMTs). The inhibition of DNMTs together with low levels of SAM results in hypomethylation of DNA and altered gene expressions. Beta oxidation of fatty acid is inhibited by generation of methyl malonic acid (MMA) from methyl malonyl-CoA within the mitochondria due to insufficiency of B12, a cofactor for methyl malonyl-CoA mutase (MCM) enzyme required for the biosynthesis of succinyl-CoA from methyl malonyl-CoA in the propionate metabolism pathway.