Oxaloacetate transport to the cytosol in gluconeogenesis

For gluconeogenesis to continue, OAA must be converted to PEP by PEPCK. PEP production in the cytosol requires transport of OAA out of mitochondria. However, there is no OAA transporter in the inner mitochondrial membrane, and OAA is first reduced to malate by mitochondrial malate dehydrogenase (MD). Malate is transported into the cytosol and reoxidized to OAA by cytosolic MD as nicotinamide adenine dinucleotide (NAD+) is reduced to NADH (Fig. 1). The NADH is used in the reduction of 1,3-bisphosphoglycerate to glyceraldehyde 3- phosphate by glyceraldehyde 3-phosphate dehydrogenase , a reaction common to glycolysis and gluconeogenesis. [Note: When abundant, lactate is oxidized to pyruvate as NAD+ is reduced. The pyruvate is transported into mitochondria and carboxylated by PC to OAA, which can be converted to PEP by the mitochondrial isozyme of PEPCK. PEP is transported to the cytosol. OAA can also be converted to aspartate that is transported into the cytosol.]

Figure 1: PEP synthesis in the cytosol. [Note: The process moves nicotinamide adenine dinucleotide (NADH) reducing equivalents required for gluconeogenesis out of mitochondria into the cytosol.] MDm and MDc = mitochondrial and cytosolic isozymes of malate dehydrogenase; GTP and GDP = guanosine tri- and diphosphates; ADP = adenosine diphosphate.