MTR and vitamin B12 deficiency: Here, the enzyme methionine synthase (MS) requires MeCbl as a cofactor to methylate the amino acid Hcy to methionine (Figure 3), which is needed to sustain adequate synthesis of proteins, DNA, and neurotransmitters.3, 48, 51, 53, 54, 55 If Cbl is deficient in the cell, plasma concentrations of methylmalonic acid—a functional marker of vitamin B12 deficiency—and Hcy will rise.