Legend: NAD+: Nicotinamide Adenine Dinucleotide; NADP+: nicotinamide adenine dinucleotide Phosphate; NADH: Reduced Nicotinamide Adenine Dinucleotide; NADPH: reduced nicotinamide adenine Dinucleotide phosphate; Star-shape indicates reaction of multiple reactants and products with various intermediates Dashed lines indicate a metabolite is present in two locations along the metabolic pathway. Bold lines indicate an irreversible reaction.

Figure 2: An overview of carbon metabolism with enzymes affected by methotrexate. MTX can be seen inhibiting many enzymes involved in glucose metabolism. The enzymes inhibited in this figure are all dehydrogenase enzymes and involved in reduction of NAD+/NADP+ to NADH/NADPH. These reduced compounds are involved in multiple cellular reactions, the regeneration of reduced glutathione being one of them. Also seen in this figure is the incorporation of asparagine and glutamine as carbon sources for the production of TCA cycle intermediates.