Pentose phosphate pathway (PPP) (PPP)

The Pentose phosphate pathway (PPP) is a critical metabolic route that branches from glycolysis to facilitate the production of nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate. The pathway is divided into an oxidative phase, which is the primary source of cellular NADPH used for reductive biosynthesis and maintaining redox balance, and a non-oxidative phase that generates pentose sugars for nucleotide and nucleic acid synthesis (StatPearls, 2023). In many pathological conditions, especially cancer, the flux through the PPP is significantly upregulated to support rapid cellular proliferation and provide a defense mechanism against reactive oxygen species (Nature Reviews Cancer, 2013). Consequently, key enzymes such as glucose-6-phosphate dehydrogenase (G6PD) and transketolase (TKT) have emerged as therapeutic targets. Inhibiting these enzymes aims to starve cells of essential building blocks and sensitize them to oxidative damage, although such interventions must carefully manage the risk of hemolytic anemia in patients with underlying genetic enzyme deficiencies (PubMed, 2020).

Other names

Hexose monophosphate shuntHMP shuntPhosphogluconate pathwayPentose shunt

Inhibition of rate-limiting enzymes within the pathway, such as glucose-6-phosphate dehydrogenase (G6PD) or transketolase, to deplete cellular NADPH and ribose-5-phosphate levels, thereby inducing oxidative stress and impairing nucleotide synthesis for DNA repair and replication.