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Figure 1 Outline of methionine/homocysteine metabolism, causes of hyperhomocysteinemia, and therapeutic options for lowering homocysteine. Vitamin coenzymes and substrates: THF, tetrahydrofolate; B₂, riboflavin; B₆, vitamin B₆ as its biologically active form, i.e., pyridoxal 5'-phosphate; and B₁₂, methyl cobalamin. Intermediate metabolite: DMG, dimethylglycine. Adapted, with permission, from Malinow et al. (48).