Produces NADPH and ribose-5-phosphate without making ATP
Expansion
Also called the hexose monophosphate shunt. It runs in the cytoplasm and produces no ATP.
Two products, two purposes
- NADPH: for reductive biosynthesis (fatty acids, cholesterol, steroids), for the respiratory burst in phagocytes, and above all for regenerating reduced glutathione to protect against oxidative damage
- Ribose-5-phosphate: for nucleotide and nucleic acid synthesis
Rate-limiting enzyme: glucose-6-phosphate dehydrogenase, inhibited by NADPH, so the pathway runs when NADPH is consumed.
Most active in tissues doing reductive synthesis or facing oxidative stress: liver, adrenal cortex, adipose tissue, lactating breast, and red cells.
G6PD deficiency, the commonest enzyme defect worldwide and X-linked, leaves red cells unable to regenerate glutathione. Oxidative stress then causes haemolysis, with Heinz bodies (denatured haemoglobin) and bite cells. Triggers are infection, fava beans, and drugs including primaquine, sulphonamides, nitrofurantoin and dapsone. Like sickle trait, it confers some protection against malaria.