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[Biochemistry](https://durgical.com/en/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

## Interactive map

**Balance:** nadph +2 CO₂ +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)](https://durgical.com/en/biochemistry/enzymes/glucose-6-phosphate-dehydrogenase/)** irreversible [Glucose 6-phosphate](https://durgical.com/en/biochemistry/molecules/glucose-6-phosphate/) + nadp → 6-Phosphoglucono-δ-lactone + [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/) It 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 →](https://durgical.com/en/conditions/glucose-6-phosphate-dehydrogenase-deficiency/)
- **Step 2 · 6-Phosphogluconolactonase** irreversible 6-Phosphoglucono-δ-lactone + H₂O → 6-Phosphogluconate It opens the lactone ring with water, leaving 6-phosphogluconate.
- **Step 3 · 6-Phosphogluconate dehydrogenase** irreversible 6-Phosphogluconate + nadp → Ribulose 5-phosphate + [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/) + CO₂ It 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-phosphate](https://durgical.com/en/biochemistry/molecules/ribose-5-phosphate/) It 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](https://durgical.com/en/biochemistry/enzymes/transketolase/)** [Ribose 5-phosphate](https://durgical.com/en/biochemistry/molecules/ribose-5-phosphate/) + Xylulose 5-phosphate ⇌ Sedoheptulose 7-phosphate + glyceraldehyde 3-phosphate It 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) →](https://durgical.com/en/conditions/wernicke-encephalopathy/)
- **Step 6 · Transaldolase** Sedoheptulose 7-phosphate + glyceraldehyde 3-phosphate ⇌ Erythrose 4-phosphate + fructose 6-phosphate It 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)](https://durgical.com/en/biochemistry/enzymes/transketolase/)** Erythrose 4-phosphate + Xylulose 5-phosphate ⇌ fructose 6-phosphate + glyceraldehyde 3-phosphate It 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

- [Glucose-6-phosphate dehydrogenase (G6PD) deficiency](https://durgical.com/en/conditions/glucose-6-phosphate-dehydrogenase-deficiency/)
- [Wernicke encephalopathy (thiamine deficiency)](https://durgical.com/en/conditions/wernicke-encephalopathy/)

## Related

- [Glucose 6-phosphate](https://durgical.com/en/biochemistry/molecules/glucose-6-phosphate/)
- [Glucose-6-phosphate dehydrogenase (G6PD)](https://durgical.com/en/biochemistry/enzymes/glucose-6-phosphate-dehydrogenase/)
- [Transketolase](https://durgical.com/en/biochemistry/enzymes/transketolase/)
- [NADPH](https://durgical.com/en/biochemistry/molecules/nadph/)
- [Ribose 5-phosphate](https://durgical.com/en/biochemistry/molecules/ribose-5-phosphate/)
- [Glycolysis](https://durgical.com/en/biochemistry/pathways/glycolysis/)
- [Glucose](https://durgical.com/en/biochemistry/molecules/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.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Pentose phosphate pathway](https://reactome.org/PathwayBrowser/#/R-HSA-71336) (Reactome, 2026); [G6PD: Glucose-6-phosphate 1-dehydrogenase (human)](https://www.uniprot.org/uniprotkb/P11413/entry) (UniProt, 2026); [TKT: Transketolase (human)](https://www.uniprot.org/uniprotkb/P29401/entry) (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.

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Source: https://durgical.com/en/biochemistry/pathways/pentose-phosphate-pathway/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/pathways/pentose-phosphate-pathway/
