FIG. 4.

NADH/NAD⁺ redox in metabolism. The enzyme GAPDH, a key step in glycolysis, reduces NAD⁺ to NADH. Depending on the functionality of mitochondria, glycolytic NADH has two different routes for reoxidation. In the presence of oxygen (the so called “aerobic glycolysis”), the reducing equivalency of NADH is transmitted into mitochondria via the MAS, comprising cytosolic plus mitochondrial isoforms of MDH working in opposing directions, and cytosolic plus mitochondrial isoforms of AST working in opposing directions. In addition the G3PDH shuttle can transfer NADH reducing equivalents into mitochondria. The mitochondrial import/export of the relevant α-keto acids and amino acids is handled by a pair of electrophoretically driven membrane exchange proteins. The end product of glycolysis, pyruvate, is imported to mitochondria and further oxidized by the Krebs' cycle. In the absence of adequate mitochondrial function (e.g., hypoxia), glycolytic NADH is instead reoxidized by LDH, generating lactic acid as a terminal product (i.e., “anaerobic glycolysis”). In either scenario, the reoxidation of NADH is an absolute requirement for glycolysis to function. AST, aspartate aminotransferase; G3PDH, glycerol-3-phosphate dehydrogenase. Color images are available online.