HMP Shunt Pathway - Steps, Regulation, Occurance and Significance

HMP Shunt Pathway: The hexose monophosphate (HMP) shunt, also called the pentose phosphate pathway or the phosphogluconate pathway, is a metabolic process that occurs alongside glycolysis. This pathway generates NADPH and produces intermediates needed for the synthesis of nucleic acids and amino acids. Below are the NEET Biology notes on the HMP shunt pathway.

HMP Shunt Pathway

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1. Oxidative Phase: In this phase, each molecule of glucose-6-phosphate is oxidized to ribulose-5-phosphate, producing NADPH and releasing CO2.

2. Non-Oxidative Phase: This phase involves the interconversion of 3, 4, 5, and 7-carbon sugars, leading to the synthesis of pentose-phosphate and other phosphate monosaccharides.

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HMP Shunt Pathway Occurs in

• NADPH: A reducing agent used in various biosynthesis reactions in the cell.
• Ribose-5-phosphate: A precursor for the synthesis of nucleotides, which are the building blocks of DNA and RNA.
• Erythrose-4-phosphate: An intermediate used in the synthesis of aromatic amino acids.

• Liver
• Red blood cells
• Adrenal cortex
• Mammary glands
• Testes
• Adipose tissue

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HMP Shunt Pathway Steps

1. Produces NADPH: This reducing equivalent is essential for biosynthetic processes such as the synthesis of fatty acids, steroids, and the regeneration of glutathione.
2. Generates ribose-5-phosphate for nucleotide synthesis: This compound is essential for building RNA and DNA.

Oxidative Phase

1. Glucose-6-phosphate dehydrogenase (G6PD) catalyzes the oxidation of glucose-6-phosphate to 6-phosphogluconate delta-lactone, producing one molecule of NADPH.
2. 6-phosphogluconate delta-lactone is hydrolyzed by 6-phosphogluconolactonase to form 6-phosphogluconate.
3. 6-phosphogluconate dehydrogenase catalyzes the decarboxylation of 6-phosphogluconate to ribulose-5-phosphate, generating another molecule of NADPH.
4. Ribulose-5-phosphate can be isomerized to ribose-5-phosphate by ribulose-5-phosphate epimerase.

Non-oxidative Phase

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Regulation of HMP Shunt Pathway

• High NADP+ levels: Activate G6PD, thereby promoting the HMP shunt when the cell requires more R5P or NADPH.
• High NADPH levels: Inhibit G6PD, slowing down the pathway when there is enough NADPH.

• Increased glucose intake or breakdown of glycogen stores: Leads to higher levels of glucose-6-phosphate, which can stimulate the pathway.

• Insulin: Promotes G6PD activity, potentially increasing the pathway's activity during fed states.
• Glucagon: Opposes the effects of insulin and may decrease HMP shunt activity during fasting.
• Thyroid hormones: Can stimulate G6PD activity.

Significance of HMP Shunt Pathway

1. Nucleic Acid Synthesis: The non-oxidative phase of the HMP shunt produces ribose-5-phosphate, a key precursor for RNA and DNA synthesis. This pathway is particularly active in rapidly dividing cells that need a steady supply of nucleotides for growth and replication.
2. NADPH Production for Biosynthesis: The oxidative phase of the HMP shunt generates NADPH, which is crucial for various anabolic reactions. NADPH is vital for the synthesis of fatty acids and cholesterol, important components of cell membranes and steroid hormones.
3. Cellular Redox Balance: NADPH is also important for maintaining cellular redox balance. It helps regenerate glutathione, an antioxidant that protects cells from oxidative damage. This is especially important for red blood cells, which are constantly exposed to reactive oxygen species.
4. Pentose Sugar Metabolism: The HMP shunt provides pentose sugars that serve as precursors for nucleotides and play roles in other cellular processes, such as amino acid metabolism.

Clinical Significance:

• Favism: This condition leads to hemolytic anemia (destruction of red blood cells) when exposed to fava beans.
• Non-spherocytic Hemolytic Anemia: A rare blood disorder characterized by the breakdown of red blood cells due to impaired antioxidant defenses.
• Glucose-6-Phosphate Dehydrogenase Deficiency: The most common enzyme deficiency related to the HMP shunt, causing various complications depending on its severity.