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Pentose phosphate pathwayPentose phosphate pathway
(hexose monophosphate shunt)(hexose monophosphate shunt)
READING:
 Har...
OBJECTIVESOBJECTIVES
 To understand the function of the pentose
phosphate pathway in production of NADPH
and ribose precu...
 The pentose phosphate pathway is an alternate route
for the oxidation of glucose.
The pentose phosphate pathway hasThe pentose phosphate pathway has
two main functionstwo main functions
 Generation of NA...
Reactions of the pentose phosphateReactions of the pentose phosphate
pathway occur in the cytosol in twopathway occur in t...
 Oxidative reactions of the
pentose phosphate pathway.
The end products are D-ribose
5-phosphate and NADPH
 In tissues requiring primarily NADPH rather than
ribose 5-phosphate, these pentose phosphates can
be recycled into gluco...
Pentose phosphate pathway protects cellsPentose phosphate pathway protects cells
against reactive oxygen species (ROS)agai...
Role of NADPH and glutathione inRole of NADPH and glutathione in
protecting cells against ROSprotecting cells against ROS
...
Glucose-6-phosphate dehydrogenaseGlucose-6-phosphate dehydrogenase
deficiency causes hemolytic anemiadeficiency causes hem...
Regulation of pentose phosphateRegulation of pentose phosphate
pathwaypathway
 The entry of glucose 6-phosphate into the ...
Pentose Phosphate Pathway (Hexose Monophosphate Shunt)
Pentose Phosphate Pathway (Hexose Monophosphate Shunt)
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Pentose Phosphate Pathway (Hexose Monophosphate Shunt)

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Reading: Harper's Biochemistry Chapter 22, Lehninger Principles of Biochemistry 3rd Ed. pp. 558-560.

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Pentose Phosphate Pathway (Hexose Monophosphate Shunt)

  1. 1. Pentose phosphate pathwayPentose phosphate pathway (hexose monophosphate shunt)(hexose monophosphate shunt) READING:  Harpers Biochemistry Chapter 22  Lehninger Principles of Biochemistry 3rd Ed. pp. 558-560
  2. 2. OBJECTIVESOBJECTIVES  To understand the function of the pentose phosphate pathway in production of NADPH and ribose precursors for nucleic acid synthesis.  To examine the importance of NADPH in protection of cells against highly reactive oxygen species.  To relate defects in the pentose phosphate pathway to disease conditions.
  3. 3.  The pentose phosphate pathway is an alternate route for the oxidation of glucose.
  4. 4. The pentose phosphate pathway hasThe pentose phosphate pathway has two main functionstwo main functions  Generation of NADPH - mainly used for reductive syntheses of fatty acids, steroids, amino acids via glutamate dehydrogenase; and production of reduced glutathione in erythrocytes and other cells. - active in liver, adipose tissue, adrenal cortex, thyroid, erythrocytes, testes, and lactating mammary gland - not active in non-lactating mammary gland and has low activity in skeletal muscle.  Production of ribose residues for nucleotide and nucleic acid synthesis.
  5. 5. Reactions of the pentose phosphateReactions of the pentose phosphate pathway occur in the cytosol in twopathway occur in the cytosol in two phasesphases  Oxidative non-reversible phase  Non-oxidative reversible phase  NADP+ , not NAD + , is used as hydrogen acceptor  1st phase1st phase - Glucose 6-phosphate undergoes dehydrogenation and decarboxylation to give a pentose, ribulose 5-phosphate, which is converted to its isomer, D-ribose 5-phosphate. - Overall equation of 1st phase: Glucose 6-phosphate + 2 NADP+ + H2O→ ribose 5-phosphate + CO2 + 2 NADPH + 2 H+
  6. 6.  Oxidative reactions of the pentose phosphate pathway. The end products are D-ribose 5-phosphate and NADPH
  7. 7.  In tissues requiring primarily NADPH rather than ribose 5-phosphate, these pentose phosphates can be recycled into glucose 6-phosphate. Overall, 6 five-carbon sugars are converted to 5 six-carbon sugars
  8. 8. Pentose phosphate pathway protects cellsPentose phosphate pathway protects cells against reactive oxygen species (ROS)against reactive oxygen species (ROS)  Molecular oxygen and partially reduced, reactive forms of oxygen. Reduction of molecular O2 in a series of one- electron steps yields superoxide, hydrogen peroxide, hydroxyl radical, and water. The intermediate, activated forms of oxygen are known as reactive oxygen species (ROS)
  9. 9. Role of NADPH and glutathione inRole of NADPH and glutathione in protecting cells against ROSprotecting cells against ROS  Role of NADPH and glutathione in protecting cells against highly reactive oxygen derivatives. Reduced glutathione (GSH) protects the cell by destroying hydrogen peroxide and hydroxyl free radicals. Regeneration of GSH from it oxidized form (GS- SG) requires the NADPH produced in the glucose 6-phosphate dehydrogenase reaction.
  10. 10. Glucose-6-phosphate dehydrogenaseGlucose-6-phosphate dehydrogenase deficiency causes hemolytic anemiadeficiency causes hemolytic anemia  Mutations present in some populations causes a deficiency in glucose 6-phosphate dehydrogenase, with consequent impairment of NADPH production.  Detoxification of H2O2 is inhibited, and cellular damage results - lipid peroxidation leads to erythrocyte membrane breakdown and hemolytic anemia.  Most G6PD-deficient individuals are asymptomatic - only in combination with certain environmental factors (sulfa antibiotics, herbicides, antimalarials, *divicine) do clinical manifestations occur. *toxic ingredient of fava beans
  11. 11. Regulation of pentose phosphateRegulation of pentose phosphate pathwaypathway  The entry of glucose 6-phosphate into the pentose phosphate pathway is controlled by the cellular concentration of NADPH  NADPH is a strong inhibitor of glucose 6- phosphate dehydrogenase  As NADPH is used in various pathways, inhibition is relieved, and the enzyme is accelerated to produce more NADPH  The synthesis of glucose 6-phosphate dehydrogenase is induced by the increased insulin/glucagon ratio after a high carbohydrate meal.
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Reading: Harper's Biochemistry Chapter 22, Lehninger Principles of Biochemistry 3rd Ed. pp. 558-560.

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