Lecture 23: Pentose Phosphate Pathway (PDF)

Lippincott’s illustrated reviews Chapter 13 – Page 145 Lecture 23 Pentose Phosphate Pathway 1  Specific Objectives By the end of this lecture students can be able to: Understand the function of pentose shunt. Explain the effect of glucose 6-P Dehydr...

Lippincott’s illustrated reviews Chapter 13 – Page 145 Lecture 23 Pentose Phosphate Pathway 1  Specific Objectives By the end of this lecture students can be able to: Understand the function of pentose shunt. Explain the effect of glucose 6-P Dehydrogenase Deficiency. 2 3  Overview The pentose phosphate pathway (also called the hexose monophosphate pathway, or 6- phosphogluconate pathway) occurs in the cytosol of the cell. It includes two, irreversible oxidative reactions, followed by a series of reversible sugar– phosphate interconversions. No ATP is directly consumed or produced in the cycle. 4 5  8 Phosphateglucan Function: Pentose phosphatepathway Pathway Hexo monophosphate Pathway The pathway provides a major portion of the body’s NADPH, which functions as a biochemical reductant. It also produces ribose 5-phosphate, required For the biosynthesis of nucleotides, and provides a mechanism for the metabolic use of five-carbon sugars obtained from the diet or the degradation of structural carbohydrates in the body. 6  Irreversible Oxidative Reactions The oxidative portion lead to the formation of ribulose 5-phosphate, CO2, and two molecules of NADPH for each molecule of glucose 6- phosphate oxidized. glucose 6 Phosphate oxidized 2 NADPH 7  Reversible No Need ATP 7 8 Site of action: This portion of the pathway is particularly important: in the liver, lactating mammary glands, and adipose, which are active in the NADPH-dependent biosynthesis of fatty acids, in the testes, ovaries, placenta and adrenal cortex, which are active in the NADPH-dependent biosynthesis of steroid hormones, and RBC in erythrocytes, which require NADPH to keep glutathione reduced. 9  Reversible Nonoxidative Reactions It occurs in all cell types synthesizing nucleotides and nucleic acids. These reversible reactions permit ribulose 5- phosphate to be converted either to ribose 5- phosphate needed for nucleotide synthesis, or to intermediates of glycolysis—fructose 6- phosphate and glyceraldehyde 3-phosphate. 10 11 Dehydrogenation of glucose 6-phosphate Glucose 6-phosphate dehydrogenase (G6PD) catalyzes an irreversible oxidation of glucose 6- phosphate to enter pentose pathway. The pentose phosphate pathway is regulated primarily at the G6PD reaction. Insulin up regulates expression of the gene for G6PD, and flux through the pathway increases in the well fed state. 12 13 14 15  Glucose 6-P Dehydrogenase Deficiency Glucose 6-phosphate dehydrogenase (G6PD) deficiency is an inherited disease characterized by hemolytic anemia caused by the inability to detoxify oxidizing agents. GGPD deficiency impair RBC to form NADPH which Leads to hemolysis Breaking down C OF RBCS G6PD deficiency is X-linked, and is, in fact, a family of deficiencies caused by more than 400 different mutations in the gene coding for G6PD. 16  Note: In addition to hemolytic anemia, a clinical manifestation of G6PD deficiency is neonatal jaundice appearing 1–4 days after birth. The jaundice, which may be severe, typically results from increased production of unconjugated bilirubin. 17  The life span of individuals with a severe form of G6PD deficiency may be somewhat shortened as a result of complications arising from chronic hemolysis. This negative effect of G6PD deficiency has been balanced in evolution by an advantage in survival— an increased resistance to falciparum malaria shown by female carriers of the mutation. 18 Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 19