Metabolic Significance of Hexose Monophosphate Shunt

The following points highlight the top five metabolic significance of hexose monophosphate shunt.

1. CO₂ is the characteristic product in this pathway which is not formed in Embden- Meyerhof pathway. This product is uti­lized for the synthesis of fatty acid and purine bases etc.

2. The reduced NADP (NADPH) formed in this pathway is used in the synthesis of fatty acids, cholesterol or steroids and in the synthesis of amino acids via glutamate dehydrogenase outside the mitochondria. The reduced NADP is also required in uronic acid pathway for the synthesis of ascorbic acid and xylulose-5-phosphate.

Ascorbic acid is not synthesized in man and other primates including guineapig. The system which utilizes reduced NADP stimulates an active degradation of glu­cose via this shunt pathway.

The reduced NADP functions in the operation of the shunt pathway in red blood cells and it has a direct correlation between the glu­coses-phosphate dehydrogenase and the fragility of red cells (susceptibility to hemolysis) when the cells are subjected to certain drugs such as primaquine and sulfonamide.

3. The pentose sugars produced in this path­way are utilized for the synthesis of nu­cleic acids and nucleotides. Skeletal muscle is incapable of synthesiz­ing ribose. This is probably accomplished by a reversal of the shunt pathway utiliz­ing fructose-6-℗, glyceraldehyde-3-℗and the enzymes transketolase and transaldolase.

4. The products fructose-6-℗and glyceraldehyde-3-℗are utilized in Embden- Meyerhof pathway for glycolysis.

5. This pathway in the erythrocytes provides reduced NADP (NADPH + H⁺) for the re­duction of oxidized glutathione (G-S-S-G) to the reduced glutathione by the en­zyme glutathione reductase.

The reduced glutathione then removes H₂O₂ from the erythrocytes by glutathione peroxidase. This reaction is important because accu­mulation of H₂O₂ may decrease the life span of erythrocytes by increasing the rate of oxidation of hemoglobin to methemoglobin.