Cytosolic alternative glucose oxidation generating NADPH (reducing power for biosynthesis + glutathione regeneration) + ribose-5-phosphate (nucleotide precursor). Oxidative branch (irreversible): G6P → 6-phosphogluconolactone → 6-phosphogluconate → ribulose-5-P, producing 2 NADPH per G6P. Non-oxidative branch (reversible): ribulose-5-P interconverts with ribose-5-P, sedoheptulose-7-P, fructose-6-P, glyceraldehyde-3-P — balances supply between nucleotide and glycolytic demands. G6PD is rate-limiting + X-linked; deficiency is the most common human enzymopathy (~400M carriers) and produces hemolytic anemia on oxidative stress (primaquine, sulfa, fava beans, dapsone, methylene blue).
Organ Systems
immune-hematologic
endocrine
Pathway Steps
glucose-6-phosphate → 6-phosphogluconolactone — via G6PD — RATE-LIMITING; X-linked; common deficiency. G6PD is the rate-limiting, NADPH-producing step and the cell’s main defense against oxidative stress (NADPH regenerates reduced glutathione). Its X-linked deficiency is the commonest human enzymopathy, causing hemolysis on oxidant exposure — fava beans, primaquine, sulfa drugs, infection.
6-phosphogluconolactone → ribulose-5-phosphate — via 6-phosphogluconate dehydrogenase (NADP+ → NADPH). 6-phosphogluconate dehydrogenase yields a second NADPH (and releases CO₂). With G6PD, this oxidative branch supplies NADPH for reductive biosynthesis (fatty acids, cholesterol) and antioxidant defense — distinct from the ATP-generating role of glycolysis.
ribulose-5-phosphate → ribose-5-phosphate — via phosphopentose isomerase (substrate for nucleotide synthesis). Phosphopentose isomerase makes ribose-5-phosphate for nucleotide and NAD/FAD/CoA synthesis. The non-oxidative branch (transketolase/transaldolase, transketolase needing thiamine/TPP) reversibly interconverts these pentoses with glycolytic intermediates, balancing NADPH vs ribose demand.