Pentose Phosphate Pathway: NADPH, Ribose-5-Phosphate and G6PD

The pentose phosphate pathway (PPP) branches off glucose-6-phosphate in the cytosol. It makes NADPH and ribose-5-phosphate. It does not make or use ATP.

Two phases

Control

Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme. It is activated by NADP⁺ and inhibited by NADPH. So the pathway runs when the cell needs NADPH.

Why the cell needs it

• NADPH is the reductant for fatty acid and cholesterol synthesis, and for keeping glutathione reduced (protection against oxidative damage).
• Ribose-5-phosphate is the sugar for nucleotide and nucleic acid synthesis.
• Immune cells use NADPH oxidase to make reactive oxygen species in the respiratory burst.

The non-oxidative phase shifts to match demand. If more NADPH than ribose is needed, the intermediates return to glycolysis; if more ribose is needed, glycolytic intermediates run backward to make it.

G6PD deficiency

Red blood cells have no mitochondria and rely on the PPP for NADPH. Without enough G6PD they cannot regenerate reduced glutathione, so oxidative stress (certain drugs, fava beans, infections) damages hemoglobin and membranes, causing hemolytic anemia with Heinz bodies. It is X-linked recessive, and carriers gain some protection against malaria.

NADPH vs NADH

NADH feeds the electron transport chain for ATP. NADPH is used in anabolic reactions. Do not interchange them.

Common traps

• Saying the PPP makes ATP. It does not.
• Mixing up the inhibitors. NADPH inhibits; NADP⁺ activates.
• Placing it in mitochondria. It is cytosolic.

One-minute recap

• Cytosolic branch from glucose-6-P: NADPH plus ribose-5-P.
• G6PD is rate-limiting; NADPH inhibits it.
• G6PD deficiency leads to hemolysis under oxidative stress.