6 min readPathway sheetOften a 10-mark answer; G6PD deficiency comes as a 5-mark note

HMP shunt (pentose phosphate pathway)

A side route for glucose-6-phosphate in the cytoplasm. It makes NADPH and ribose-5-phosphate, but no ATP. G6PD is the key enzyme.

WhereCytoplasm of liver, adipose tissue, RBCs, adrenal cortex, lactating mammary gland

Main productsNADPH + ribose-5-phosphate

ATP madeNone directly

Control pointGlucose-6-phosphate dehydrogenase (G6PD)

Oxidative phase (one-way)

HMP = hexose monophosphate. NADPH is a hydrogen carrier like NADH, but it is used for building molecules and for protection, not for ATP. Each glucose-6-P here gives 2 NADPH and 1 CO2. The starred step is rate-limiting.

1★
Glucose-6-P → 6-Phosphogluconolactone
Glucose-6-phosphate dehydrogenase (G6PD) · makes NADPH · rate-limiting
2
6-Phosphogluconolactone → 6-Phosphogluconate
Lactonase · adds water
3
6-Phosphogluconate → Ribulose-5-P + CO2
6-Phosphogluconate dehydrogenase · makes NADPH · releases CO2

★ one-way, controls the pace

Non-oxidative phase (reversible)

The 5-carbon sugars are reshuffled. Pentoses not needed for nucleotides are turned back into glycolysis intermediates. The starred enzyme needs thiamine.

1
Ribulose-5-P ⇌ Ribose-5-P
Ribose-5-phosphate isomerase · ribose for DNA, RNA, ATP, NAD, FAD
2
Ribulose-5-P ⇌ Xylulose-5-P
Ribulose-5-phosphate epimerase
3★
Xylulose-5-P + Ribose-5-P ⇌ Glyceraldehyde-3-P + Sedoheptulose-7-P
Transketolase · moves 2 carbons · needs TPP (thiamine)
4
Sedoheptulose-7-P + Glyceraldehyde-3-P ⇌ Fructose-6-P + Erythrose-4-P
Transaldolase · moves 3 carbons
5★
Xylulose-5-P + Erythrose-4-P ⇌ Fructose-6-P + Glyceraldehyde-3-P
Transketolase · needs TPP again

★ one-way, controls the pace

Overall balance (3 glucose-6-P)

Start3 glucose-6-P (18 carbons)

NADPH made6 NADPH

CO2 released3 CO2 (3 carbons)

Sugars returned to glycolysis2 fructose-6-P + 1 glyceraldehyde-3-P (15 carbons)

ATP madeNone directly

What the products are used for

BuildingNADPH supplies hydrogen to make fatty acids, cholesterol and steroid hormones. So the shunt is busy in liver, adipose tissue, adrenal cortex and the lactating mammary gland (milk fat).

ProtectionNADPH keeps glutathione in its reduced form, so it can destroy hydrogen peroxide. In red blood cells the shunt is the only source of NADPH, so it protects their membranes.

Nucleotides and moreRibose-5-P builds DNA, RNA, ATP, NAD and FAD. NADPH also runs cytochrome P450 (drug detoxification in the liver) and helps white blood cells kill bacteria.

If a cell needs ribose but not NADPH, the reversible non-oxidative steps make ribose-5-P from fructose-6-P and glyceraldehyde-3-P.

Nutrition link

G6PD deficiency is the most common enzyme deficiency in the world and is seen in many Indian communities. Red blood cells cannot make enough NADPH, so after fava beans (broad beans), drugs like primaquine (antimalarial) or sulpha drugs, or an infection, they burst: haemolytic anaemia. Thiamine is needed by transketolase; red-cell transketolase activity is a lab test for thiamine status.

Exam angle

10 marks: “Describe the HMP shunt and its significance.” Write both phases with enzymes, give the overall balance, then the uses of NADPH and ribose-5-P, and G6PD deficiency.

5 marks: “Write a note on G6PD deficiency.” Inherited lack of G6PD → low NADPH → little reduced glutathione → red cells burst after fava beans, primaquine or infection.

2 marks: “Name two tissues where the HMP shunt is very active.” Liver and adipose tissue (also adrenal cortex, lactating mammary gland and red blood cells).

Remember it

Two products, two jobs. NADPH builds (fat, cholesterol, steroids) and guards (glutathione in red cells); ribose-5-P builds nucleotides. No ATP.