For a 6-mark MBBS Biochemistry question on HMP shunt, write about 2 to 2½ handwritten pages. Draw a clear flowchart. The examiner usually expects: definition, site, phases with key enzymes, functions of NADPH/ribose-5-phosphate, and clinical importance.
Model answer for university exam
Hexose Monophosphate Shunt (HMP shunt)
Also called: Pentose phosphate pathway or phosphogluconate pathway.
Definition:
HMP shunt is an alternative pathway of glucose oxidation that occurs in the cytosol. It starts with glucose-6-phosphate and produces NADPH, pentose sugars, and CO₂. ATP is neither produced nor utilized directly in this pathway.
Site
It occurs in the cytoplasm of all cells, but is particularly active in:
- Liver
- Adipose tissue
- Lactating mammary gland
- Adrenal cortex
- Gonads
- Thyroid
- Red blood cells
- Phagocytic cells
Steps / phases
The HMP shunt has two phases:
1. Oxidative phase - irreversible
This phase produces NADPH.
Glucose-6-phosphate
│ Glucose-6-phosphate dehydrogenase
│ NADP+ → NADPH
↓
6-Phosphoglucono-δ-lactone
│ Lactonase
↓
6-Phosphogluconate
│ 6-Phosphogluconate dehydrogenase
│ NADP+ → NADPH + CO₂
↓
Ribulose-5-phosphate
Key regulatory enzyme: Glucose-6-phosphate dehydrogenase (G6PD)
2. Non-oxidative phase - reversible
Ribulose-5-phosphate
↓
Ribose-5-phosphate + Xylulose-5-phosphate
↓
Fructose-6-phosphate + Glyceraldehyde-3-phosphate
↓
Enter glycolysis
Important enzymes:
- Ribose-5-phosphate isomerase
- Transketolase - requires thiamine pyrophosphate, TPP
- Transaldolase
Functions / significance
A. Functions of NADPH
- Required for fatty acid synthesis.
- Required for synthesis of cholesterol, steroid hormones and bile acids.
- Maintains glutathione in its reduced form (GSH) in RBCs, thereby protecting RBCs from oxidative damage.
- Used in cytochrome P450 system for detoxification of drugs and xenobiotics.
- Required for respiratory burst in phagocytes for killing microorganisms.
- Required for reduction of oxidized glutathione and methemoglobin.
B. Functions of ribose-5-phosphate
- Required for synthesis of nucleotides, nucleic acids (DNA and RNA), ATP, NAD⁺, FAD and coenzyme A.
Clinical importance
G6PD deficiency
G6PD deficiency decreases production of NADPH in RBCs. Therefore, reduced glutathione cannot be regenerated adequately. On exposure to oxidant stress, RBCs undergo hemolysis, causing hemolytic anemia.
Oxidant stress may be caused by:
- Infections
- Fava beans
- Sulfonamides
- Primaquine and other oxidant drugs
Peripheral smear may show Heinz bodies and bite cells.
One-line conclusion
Thus, the HMP shunt is important mainly for production of NADPH and ribose-5-phosphate, rather than ATP.
How to score all 6 marks
| Part | What to write | Marks expected |
|---|
| Definition, alternative names, site | 3-4 lines | 1 |
| Oxidative phase with diagram and NADPH | 1.5 | |
| Non-oxidative phase with transketolase | 1 | |
| Functions of NADPH and ribose-5-P | 1.5 | |
| G6PD deficiency | 1 | |
High-yield presentation tip: Underline NADPH, ribose-5-phosphate, G6PD, reduced glutathione, and hemolytic anemia. A tidy pathway diagram is more scoring than writing long paragraphs.