The oxoglutarate reductive carboxylation pathway: A review

Acetyl Coenzyme A is required for a variety of processes in the cytosol such as lipogenesis as well as a variety of acetylations. One mechanism whereby these acetyl groups are provided is a metabolic pathway by which oxoglutarate (or glutamate) is translocated from the mitochondria and is reductively carboxylated to isocitric acid in the cytosol. This is then converted to citrate which cleaved to acetyl CoA and oxaloacetate by ATP citrate lyase. This pathway has been termed the Oxoglutarate Reductive Carboxylation Pathway. The C 2 units produced are used for such acetyl CoA requiring processes as fatty acid and cholesterol biosynthesis; the C 4 units are used in some tissues for gluconeogenesis. In tissues other than those of the nervous system the contribution of carbon units by this pathway is profoundly influenced by the nutritional state of the animal. In starved animals, where fatty acid synthesis is curtailed, the conversion of labeled glutamate to C 4 and C 2 units for gluconeogenesis and fatty acids is severely depressed. In carbohydrate-fed animals, or with animals maintained under conditions which stimulate fatty acid synthesis, glutamate conversion by this pathway may reach 50–60% of the radiolabeled glutamate utilized. Other conditions which influence the function of this pathway are the developmental stage of the organism such as in the fetal vs adult ruminant or the developmental stage of the brain, the presence or absence of insulin, and the yearly cycle of hibernating animals.