Reference Work Entry

Handbook of Neurochemistry and Molecular Neurobiology

pp 41-62


1.3 Pentose Phosphate Pathway and NADPH Metabolism

  • R. Dringen
  • , H. H. Hoepken
  • , T. Minich
  • , C. Ruedig


The pentose phosphate pathway (PPP) is an essential metabolic pathway in the glucose metabolism of the brain. Under normal conditions, the PPP plays a minor part in total glucose consumption. However, its products NADPH and ribose-5-phosphate have important functions in brain cells as electron donor for various enzymatic reactions and as precursor for the synthesis of nucleotides, respectively. This chapter discusses properties of PPP enzymes and the regulation of the flux of metabolites through the PPP in brain and neural cells. The functions of the PPP in neural cells are described with special emphasis on the roles of cytosolic NADPH in brain cells. This reduced cofactor is highly important for the antioxidative defense of brain cells by glutathione (GSH) redox cycling. In addition, NADPH provides reduction equivalents for biosynthetic reactions as well as for the generation of nitric oxide and superoxide. Finally, evidence for a connection between human diseases and alterations in the activities of PPP enzymes in brain are presented.