New roles for gluconeogenesis in vertebrates

Gluconeogenesis and glycolysis are the two major opposing metabolic pathways in central carbon metabolism. In verte-brates, biomass generation has been linked primarily to glycolysis, whereas gluconeogenesis has been classically regarded to be limited to specialized gluconeogenic organs. Studies from the recent years, however, show that gluconeo-genesis is used by peripheral tissues, immune cells, and cancer cells of different origins to generate glycolytic/gluco-neogenic intermediates for biosynthetic reactions. Moreover, phosphoenolpyruvate carboxykinase, which mediates the initial step in gluconeogenesis, has been found to exert nonmetabolic functions, which may play a role in different cancers. The present review highlights the implications of the novel findings in health and disease.