PENTOSE PATHWAY

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BIOC 460 - DR. TISCHLER LECTURE 30
PENTOSE PATHWAY ANTIOXIDANTS
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OBJECTIVES

• Pentose-phosphate pathway
• a) oxidative and non-oxidative branches
• b) cofactor with each branch
• c) how oxidative branch is regulated
• d) three modes of the pentose phosphate pathway
  in terms of roles of the potential endproducts
  of each mode.

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• Antioxidant functions
• a) major active oxygen species rank
  according to relative reactivity
• b) enzymes that remove peroxides and
  superoxide radicals from a cell and name their
  cofactor.
• c) why a defect of glucose-6-phosphate
  dehydrogenase in the red blood cell might lead
  to loss of membrane integrity.
• d) relationships between components of
  antioxidant cascade including the reactions
  involved

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Functions of Pentose Phosphate Pathway

• NADPH for biosynthetic pathways (e.g., synthesis
  of fatty acids and cholesterol)
• 2) NADPH for maintaining glutathione in its
  reduced state (see discussion of glutathione
  later)
• 3) Pentose sugar for synthesis of nucleic
  acids

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glycolytic intermediates
Figure 1. The pentose phosphate pathway
containing an oxidative and a non-oxidative
branch
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Nucleic acids
Ribulose 5-P
Ribose 5-P
Xylulose 5-P
Glyceraldehyde 3-P
Transketolase
Transketolase
Non-oxidative Branch
Sedoheptulose 7-P
Glyceraldehyde 3-P
Transaldolase
Fructose 6-P
Erythrose 4-P
Fructose 6-P
Ribose-5-P is the sugar required for the
synthesis of nucleic acids
Figure 2. Using the non-oxidative branch of the
pentose pathway to produce ribose-5-phosphate for
the nucleic acid pathways (Mode 1).
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NADPH
NADP
6-Phosphogluconate
Glucose 6-P
NADP
NADPH
CO2
Ribulose 5-P
Ribose 5-P
Nucleic acids
Figure 3. Using the oxidative branch of the
pentose pathway to produce NADPH for biosynthetic
reactions and ribose-5-phosphate for producing
nucleic acids (Mode 2).
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NADPH
NADP
Glucose 6-P (3)
6-Phosphogluconate
NADP
Oxidative Branch
NADPH
CO2
Ribulose 5-P (3)
Glyceraldehyde 3-P (1)
Ribose 5-P (1)
Xylulose 5-P (2)
Non- oxidative Branch
back to glucose-6-P or to glycolysis
Sedoheptulose 7-P (1)
Glyceraldehyde 3-P (1)
Erythrose 4-P (1)
Fructose 6-P (1)
Fructose 6-P (1)
back to glucose-6-P or to glycolysis
Figure 4. Using the oxidative branch to produce
NADPH for biosynthesis and returning ribulose-5-P
to glycolytic intermediates (mode 3)
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NUTRITIONAL PREMISE THIAMINE (VITAMIN B1)

• used by transketolase, PDH, ?KgDH
• deficiency affects nucleic acid synthesis/energy
  metabolism
• Wernicke-Korsakoff syndrome observed in
  alcoholics due to poor diet
• thiamine deficiency in individuals on high CHO
  diet (e.g., rice) causes beriberi
• patients tire easily
• cardiac decompensation
• energy depletion on high CHO diet

Sergei Korsakoff
Carl Wernicke
Patient with beriberi
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Table 1. ACTIVE OXYGEN SPECIES
Reactivity AO Species
Least singlet oxygen
superoxide radical anion (O2-?)
Moderate hydrogen peroxide (HOOH)
lipid peroxyl radical (LOO?)
Most hydroxyl radical (OH?)
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Figure 5. Reactions of glutathione reduction
and oxidation
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SUMMARY OF ANTI-OXIDANT ENZYMES
Glutathione peroxidase 2 GSH H2O2 ? GSSG 2
H2O Uses selenium as a cofactor
Catalase 2 H2O2 ? H2O O2
Lipid Peroxidase removes LOOH
Superoxide dismutase 2 O2-? 2H ? H2O2 O2
Mitochondrial - Mn2 cofactor Cytoplasmic
Cu2-Zn2 cofactors mutations associated with
familial amyotrophic lateral sclerosis (FALS)
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Figure 6. Antioxidant cascade Reduced
forms/reduction Oxidized forms/oxidation