HMP SHUNT
➡️The HMP (Hexose Monophosphate Pathway) Shunt, also known as the
🔺Pentose Phosphate Pathway or
🔺Phosphogluconate Pathway, is a biochemical pathway that serves as an alternative metabolic pathway for glucose.
💡The First Phase is Oxidative and Irreversible.
🔹Glucose-6-phosphate (G6P) is converted via series of steps into Ribulose-5-phosphate.
🔹The most important catalytic enzyme is Glucose-6-phosphate Dehydrogenase (G6PD), which produces NADPH in the process.
🔹This is the major source of NADPH in the cell, and decreased NADPH can be seen in G6PD Deficiency (G6PD Deficiency is a X-linked recessive disorder that causes episodic breakdown of red blood cells).
💡The Second Phase is Non-oxidative and Reversible,
🔹 Involves transketolase as a major enzyme.
🔹Ribulose-5-phosphate is converted into Ribose-5-phosphate, which can undergo further reactions to produce Fructose-6-phosphate and Glyceraldehyde-3-phosphate.
🔹Ribose-5-phosphate is an important precursor to PRPP (phosphoribosyl pyrophosphate (PRPP) catalyzed by PRPP-synthetase) in the Purine and Pyrimidine Synthesis pathways.
🔹 Of note, the action of transketolase requires Vitamin B1/Thiamine as a cofactor.
🎯 POINTS TO PONDER HMP SHUNT:
💡Clinical Correlation—HMP Pathway
Glucose 6 Phosphate Dehydrogenase Deficiency
🔺Most common enzyme deficiency in human beings.
X-linked recessive
🔺Manifest as
• Hemolytic Anemia
• Methemoglobinemia
🔺Due to decrease in NADPH which clears the free radicals in the
RBCs and keep the iron in the hemoglobin in the reduced state.
👉These people are sensitive to certain drugs like
• Primaquine, Aspirin, Sulfadrugs
• Consumption of favabeans (vicia fava) can also precipitate hemolysis. (Favism)
1️⃣ Metabolites in HMP Shunt are all except:
a. Glycerol-3-phosphate
b. Sedoheptulose-7-phosphate
c. Glyceraldehyde-3-phosphate
d. Xylulose-5-phosphate
Ans. a. Glycerol 3 Phosphate
💡Metabolites in HMP Shunt Pathway
• Glucose-6-phosphate
• 6-Phosphogluconate
• Ribulose-5-Phosphate
• Xylulose-5-Phosphate
• Ribose-5-Phosphate
• Glyceraldehyde-3-Phosphate
• Sedoheptulose-7-Phosphate
• Fructose-6-phosphate
• Erythrose 4 Phosphate.
2️⃣ NADPH is produced by:
a. Glycolysis
b. Citric acid cycle
c. HMP shunt
d. Glycogenesis
Ans. c. HMP shunt
💡Key points to remember in HMP (Pentose Phosphate) Pathway
• Main source of NADPH and Pentoses
• Two transketolation and one transaldolation reactions are involved
• No ATP is produced
• CO2 is produced in this pathway and not in glycolytic pathway
• Deficiency of Glucose-6-phosphate dehydrogenase is a major cause of acute hemolysis in erythrocytes
• NADPH is used for reductive biosynthetic pathways, like fatty acid synthesis, steroid synthesis, Amino acids by Glutamate dehydrogenase
• NADPH is required for regeneration of reduced Glutathione, that clears free radicals from erythrocytes and lens.
3️⃣ Which of the following metabolic pathways does not generate ATP:
a. Glycolysis
b. TCA Cycle
c. Fatty Acid Oxidation
d. HMP Pathway
Ans. d. HMP Pathway
4️⃣ Severe thiamine deficiency is associated with:
a. Decreased RBC transketolase activity
b. Increased clotting time
c. Decreased RBC transaminase activity
d. Increased xanthic acid excretion
Ans. a. Decreased RBC transketolase activity
Thiamine is a coenzyme of Erythrocyte transketolase so its activity is decreased if Thiamine deficiency.
5️⃣ Reduced NADPH is produced from which pathway:
a. Krebs cycle
b. Anerobic glycolysis
c. Uronic acid pathway
d. Hexose monophosphate pathway
Ans. d. HMP pathway.