Pentose phosphate pathway and ATP synthesis pathways (PPP/ATP synthesis)

The pentose phosphate pathway (PPP) and ATP synthesis pathways, including glycolysis and oxidative phosphorylation, constitute the core metabolic framework of the cell. The PPP is essential for generating NADPH, which maintains redox homeostasis and supports reductive biosynthesis, and ribose-5-phosphate for nucleotide production (StatPearls, 2023). ATP synthesis pathways, primarily oxidative phosphorylation within the mitochondria, provide the necessary energy for cellular maintenance and signaling (NIH, 2022). In many diseases, particularly cancer, these pathways are significantly altered to favor rapid biomass accumulation and survival under stress, a process known as metabolic reprogramming (Nature Reviews Cancer, 2011). While these pathways are not single targets themselves, they contain numerous enzymes that serve as therapeutic vulnerabilities. Drugs like metformin or specific G6PD inhibitors aim to exploit these dependencies to treat metabolic and oncological conditions (Journal of Clinical Investigation, 2013).

Other names

Phosphogluconate pathwayHexose monophosphate shuntOxidative phosphorylationGlycolysisCellular respirationEnergy metabolism

Drugs typically target specific rate-limiting enzymes or protein complexes within these pathways, such as inhibiting Complex I of the electron transport chain to disrupt ATP synthesis or inhibiting glucose-6-phosphate dehydrogenase to impair the pentose phosphate pathway.