Biochemistry · Metabolic pathway
Pentose phosphate pathway !
This pathway uses glucose 6-phosphate to make NADPH, which protects cells from oxidative damage, and ribose for DNA and RNA.
Updated 2026-11-01
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Balance: nadph +2CO₂ +1
Key facts
- Oxidative phase (steps 1–3), irreversible: each glucose 6-phosphate yields 2 NADPH and 1 CO₂, leaving ribulose 5-phosphate. It makes and uses no ATP.
- Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting step; NADP⁺ activates it and NADPH holds it back.
- Non-oxidative phase (steps 4–7), reversible: transketolase (with thiamine, B1) and transaldolase swap carbons and return fructose 6-phosphate and glyceraldehyde 3-phosphate to glycolysis.
- It is very active in liver, adipose tissue, adrenal cortex, lactating mammary gland and red cells: wherever fatty acids and steroids are made or antioxidant defence is needed.
- It takes place in the cytosol.
In detail
- NADPH keeps glutathione reduced (glutathione reductase); reduced glutathione removes hydrogen peroxide in the red cell.
- If the cell needs more ribose than NADPH (a dividing cell), the non-oxidative phase runs backwards and makes ribose 5-phosphate from fructose 6-phosphate and glyceraldehyde 3-phosphate, skipping the oxidative phase.
- If it needs more NADPH than ribose, the pentoses return to glycolysis as fructose 6-phosphate and glyceraldehyde 3-phosphate, which can be recycled to glucose 6-phosphate.
- NADPH is also used to make fatty acids, cholesterol and steroids, by neutrophil NADPH oxidase and by cytochrome P450.
- Overall when everything returns to glycolysis: 3 glucose 6-phosphate → 6 NADPH + 3 CO₂ + 2 fructose 6-phosphate + 1 glyceraldehyde 3-phosphate.
- Also called
- Hexose monophosphate shunt, Phosphogluconate pathway
Regulation
- The NADP⁺/NADPH ratio controls G6PD: when NADPH is used up (fat synthesis, oxidative stress) the pathway speeds up.
- Insulin and a carbohydrate-rich diet increase G6PD synthesis in liver and adipose tissue.
- The non-oxidative phase is regulated by substrate availability.
The steps, one by one
- Step 1 · Glucose-6-phosphate dehydrogenase (G6PD) irreversible Glucose 6-phosphate + nadp → 6-Phosphoglucono-δ-lactone + NADPHIt oxidises glucose 6-phosphate and makes the first NADPH: the rate-limiting, committed step.If it fails: G6PD deficiency is the world's most common enzyme defect: acute haemolysis with oxidants and neonatal jaundice. Glucose-6-phosphate dehydrogenase (G6PD) deficiency →
- Step 2 · 6-Phosphogluconolactonase irreversible 6-Phosphoglucono-δ-lactone + H₂O → 6-PhosphogluconateIt opens the lactone ring with water, leaving 6-phosphogluconate.
- Step 3 · 6-Phosphogluconate dehydrogenase irreversible 6-Phosphogluconate + nadp → Ribulose 5-phosphate + NADPH + CO₂It oxidises and decarboxylates: the second NADPH and one CO₂ leave, and a pentose, ribulose 5-phosphate, remains.
- Step 4 · Ribose-5-phosphate isomerase Ribulose 5-phosphate ⇌ Ribose 5-phosphateIt turns the ketose into an aldose: ribose 5-phosphate goes to nucleotides (or on through the non-oxidative phase). Another part of the ribulose 5-phosphate becomes xylulose 5-phosphate (epimerase).
- Step 5 · Transketolase Ribose 5-phosphate + Xylulose 5-phosphate ⇌ Sedoheptulose 7-phosphate + glyceraldehyde 3-phosphateIt moves two carbons from xylulose 5-phosphate to ribose 5-phosphate: sedoheptulose 7-phosphate (7 C) and glyceraldehyde 3-phosphate (3 C) come out.If it fails: In thiamine deficiency transketolase loses activity: the basis of the red cell transketolase test. Wernicke encephalopathy (thiamine deficiency) →
- Step 6 · Transaldolase Sedoheptulose 7-phosphate + glyceraldehyde 3-phosphate ⇌ Erythrose 4-phosphate + fructose 6-phosphateIt moves three carbons from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate: erythrose 4-phosphate and fructose 6-phosphate come out.If it fails: Transaldolase deficiency is very rare: liver damage from birth.
- Step 7 · Transketolase (second time) Erythrose 4-phosphate + Xylulose 5-phosphate ⇌ fructose 6-phosphate + glyceraldehyde 3-phosphateIt moves two carbons from another xylulose 5-phosphate to erythrose 4-phosphate: fructose 6-phosphate and glyceraldehyde 3-phosphate come out and return to glycolysis.
Clinical notes
- G6PD deficiency leaves the red cell without NADPH: oxidants such as fava beans, primaquine, dapsone or an infection cause haemolysis with Heinz bodies.
- Red cell transketolase activity measures thiamine (B1) status; it falls in alcoholism and Wernicke encephalopathy.
- Without NADPH, neutrophil NADPH oxidase cannot produce the respiratory burst (chronic granulomatous disease when that oxidase fails).
Related conditions
Related
- Glucose 6-phosphate
- Glucose-6-phosphate dehydrogenase (G6PD)
- Transketolase
- NADPH
- Ribose 5-phosphate
- Glycolysis
- Glucose
Test yourself
Think of the answer, then tap the question to see it.
What are the two main products of the pentose phosphate pathway?
NADPH (antioxidant defence and fat and steroid synthesis) and ribose 5-phosphate (nucleotides).
What is the rate-limiting enzyme and what regulates it?
G6PD; NADP⁺ activates it and NADPH inhibits it.
Which vitamin does transketolase need?
Thiamine (B1), as thiamine pyrophosphate; this is why red cell transketolase measures B1 deficiency.
Why does the red cell depend so much on this pathway?
It is its only source of NADPH, which keeps glutathione reduced to remove peroxides.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Pentose phosphate pathway (Reactome, 2026); G6PD: Glucose-6-phosphate 1-dehydrogenase (human) (UniProt, 2026); TKT: Transketolase (human) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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Representative model, for educational purposes only.