# HMP Shunt (Pentose Phosphate Pathway)

> HMP shunt in MBBS Biochemistry: oxidative and non-oxidative phases, NADPH functions, transketolase, G6PD deficiency and haemolysis.

- Canonical URL: https://prepelephant.com/topics/mbbs/biochemistry/hmp-shunt
- Exam / course: MBBS · Subject: Biochemistry
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-02
- Last updated: 2026-10-02
- How to cite: "HMP Shunt (Pentose Phosphate Pathway)", PrepElephant, https://prepelephant.com/topics/mbbs/biochemistry/hmp-shunt

## Direct answer

Oxidising glucose-6-phosphate to ribulose-5-phosphate, the hexose monophosphate (HMP) shunt generates the cell's reducing power rather than ATP: the oxidative phase, catalysed by the rate-limiting glucose-6-phosphate dehydrogenase and then 6-phosphogluconate dehydrogenase, produces two molecules of NADPH per glucose and liberates carbon dioxide. The non-oxidative phase, led by thiamine-pyrophosphate-dependent transketolase and transaldolase, interconverts sugars so that three pentoses can be rearranged into two hexoses and a triose, feeding ribose-5-phosphate to nucleotide synthesis. NADPH then services fatty acid and steroid synthesis, keeps glutathione reduced, powers the respiratory burst, and supports cytochrome P450 and nitric oxide synthesis — tissues doing lipogenesis (liver, mammary gland, adipose) and red cells run the shunt hardest.

## What you must remember

- **Oxidative phase enzymes:** glucose-6-phosphate dehydrogenase (G6PD, rate-limiting, NADP+-dependent and inhibited by NADPH) and 6-phosphogluconate dehydrogenase; net yield two NADPH plus one carbon dioxide per glucose-6-phosphate.
- **Non-oxidative enzymes:** transketolase (TPP-dependent, the index enzyme of thiamine deficiency) and transaldolase; ribose-5-phosphate is the product cells extract for DNA and RNA, ATP, NAD and coenzyme A.
- **NADPH versus NADH:** NADPH is used for reductive biosynthesis and antioxidant defence and is not funnelled into oxidative phosphorylation — the two pools stay separate.
- **Tissue logic:** liver, adipose, lactating mammary gland, adrenal cortex, gonads, red cells and phagocytes are shunt-rich; muscle is comparatively poor (it takes its ribose from intermediates).
- **G6PD deficiency:** X-linked, the commonest human enzymopathy affecting hundreds of millions; haemolysis triggered by primaquine, sulphonamides, nitrofurantoin, naphthalene mothballs, fava beans and infections.
- **Laboratory picture of a haemolytic episode:** bite cells and blister cells on smear, Heinz bodies (denatured haemoglobin) on supravital staining, haemoglobinuria, and a positive fluorescent spot test (NADPH failure under ultraviolet light).
- **Respiratory burst:** membrane NADPH oxidase reduces oxygen to superoxide in phagocytes; its inherited defect causes chronic granulomatous disease with recurrent catalase-positive infections such as staphylococci.

## A typical exam case

A young soldier given primaquine for falciparum malaria develops dark urine and falling haemoglobin two days later. Reason it out: the drug's oxidant stress generates peroxide in red cells; a G6PD-deficient erythrocyte cannot regenerate reduced glutathione because its only NADPH source is the shunt (mature red cells lack mitochondria), so sulphydryl groups in haemoglobin oxidise, precipitating as Heinz bodies that the spleen bites out, producing bite cells. Because older red cells carry the least enzyme, the haemolysis is self-limited — the reticulocyte cohort that replaces them is enzyme-richer, an exam-worthy paradox in which the patient "recovers despite continuing the drug."

Then separate the mimics: chronic granulomatous disease shares the NADPH theme but in neutrophils (negative nitroblue tetrazolium test, absent burst), while hereditary spherocytosis gives spherocytes and a positive osmotic fragility. In Indian practice, screen before prolonged primaquine or dapsone therapy in endemic regions, since the Mediterranean and African variants differ in residual activity.

## High-yield viva angles

Asked "why does the red cell need the shunt if glycolysis supplies its ATP," answer with glutathione: it must constantly reduce oxidised glutathione at the cost of NADPH, and with no mitochondria the shunt is the sole source — the entire haemolytic phenotype flows from this single dependency. A second favourite: why does the shunt not make ATP, and is that a defect? It is a deliberate trade — carbon flows to pentoses and reducing equivalents rather than to pyruvate, and cells can even run the non-oxidative phase in reverse to meet ribose demand without carbon dioxide loss. Finally, know that the erythrocyte shunt handles roughly 5-10 percent of glucose flux normally, rising when oxidant challenge appears.

## Frequently asked questions

### What is the rate-limiting enzyme of the HMP shunt?

Glucose-6-phosphate dehydrogenase, whose NADPH product inhibits it and whose NADP+ substrate induces it, in classic feedback fashion.

### How many NADPH molecules are produced per glucose entering the oxidative phase?

Two NADPH per glucose-6-phosphate, along with one carbon dioxide and ribulose-5-phosphate.

### Why are red cells selectively damaged in G6PD deficiency?

Mature erythrocytes lack mitochondria, so the HMP shunt is their only NADPH source; without it, oxidant stress cannot be neutralised through reduced glutathione and haemoglobin precipitates as Heinz bodies.

### Which enzyme of the non-oxidative phase needs thiamine?

Transketolase, a TPP-dependent enzyme; measuring its activation coefficient with added thiamine pyrophosphate is a functional test of thiamine status.

### What is the function of NADPH in phagocytic cells?

Membrane NADPH oxidase uses it to generate superoxide radicals of the respiratory burst, whose inherited failure causes chronic granulomatous disease.