Pentose phosphate pathway (PPP)

The pentose phosphate pathway (PPP) is a cytosolic metabolic pathway parallel to glycolysis, primarily responsible for generating NADPH and ribose 5-phosphate, a precursor for nucleotide synthesis[3][5][6][7]. It has two phases: the oxidative phase, which irreversibly produces NADPH (critical for reductive biosynthesis, antioxidant defense, and maintaining redox homeostasis), and the non-oxidative phase, which produces ribose 5-phosphate and shuttles intermediates between the PPP and glycolysis[2][7]. The PPP is crucial in tissues with high rates of lipid and nucleotide synthesis (e.g., liver, adrenal cortex, lactating mammary gland, and red blood cells)[5]. The pathway's proper function is necessary to counteract oxidative stress, support biosynthesis, and provide metabolic flexibility. Dysfunction (especially a deficiency in glucose-6-phosphate dehydrogenase) can lead to hemolytic anemia and increased susceptibility to oxidative damage, while upregulation is implicated in cancer and metabolic disorders[1][6]. The pentose phosphate pathway is not a single molecule, receptor, or protein, but rather a series of enzymatic reactions. As such, it is not directly a therapeutic target in the same sense as an enzyme or receptor, although individual enzymes (e.g., G6PD) within the PPP are targets for drug development or biomarkers for disease[1][4][6].

Other names

Phosphogluconate pathwayHexose monophosphate shuntHMP shuntPentose phosphate shunt