Pentose Phosphate Pathway - Lecture 23

Pentose Phosphate Pathway (Lecture 23)

• The pentose phosphate pathway, also called the hexose monophosphate pathway or 6-phosphogluconate pathway, occurs in the cytosol of cells.
• It involves two irreversible oxidative reactions followed by reversible sugar-phosphate interconversions.
• No ATP is directly consumed or produced in the pathway.

Specific Objectives

• Understand the function of the pentose shunt.
• Explain the effect of glucose 6-P dehydrogenase deficiency.

Pathway Overview

• The pentose pathway is a shunt from glycolysis.
• The pathway generates NADPH, a crucial biochemical reductant.
• It produces ribose-5-phosphate, essential for nucleotide synthesis.
• It provides a mechanism to utilize five-carbon sugars from the diet or carbohydrate breakdown.

Irreversible Oxidative Reactions

• The oxidative portion produces ribulose-5-phosphate, CO2, and two NADPH molecules per glucose-6-phosphate oxidized.
• One glucose-6-phosphate oxidized yields two NADPH.

Oxidative Stages

• Glucose-6-phosphate is oxidized by glucose-6-phosphate dehydrogenase.
• 6-phosphogluconolactone is hydrolyzed by gluconolactonase.
• 6-phosphogluconate is oxidized by 6-phosphogluconate dehydrogenase, producing CO2.
• Resulting ribulose-5-phosphate can be converted to ribose-5-phosphate (necessary for nucleotide synthesis).

Site of Action

• Important in liver, lactating mammary glands, and adipose tissue for fatty acid synthesis.
• Important in testes, ovaries, placenta, and adrenal cortex for steroid hormone synthesis.
• Important in red blood cells (RBCs) to maintain reduced glutathione.

Reversible Nonoxidative Reactions

• Occurs in all cell types synthesizing nucleotides and nucleic acids.
• Enables ribulose-5-phosphate conversion to ribose-5-phosphate for nucleotide synthesis, or to glycolysis intermediates.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

• G6PD deficiency is an inherited disease characterized by hemolytic anemia due to the inability to detoxify oxidizing agents.
• G6PD deficiency inhibits RBCs from producing NADPH, which leads to hemolysis.
• This deficiency is X-linked and results from multiple mutations.
• Symptoms can include neonatal jaundice and a shorter lifespan in severe cases.
• Resistance to falciparum malaria is observed in female carriers.

This quiz covers the pentose phosphate pathway, highlighting its significance in cellular metabolism. Understand the function of the pathway, its oxidative reactions, and the implications of glucose 6-P dehydrogenase deficiency. Test your knowledge on the generation of NADPH and ribose-5-phosphate.