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Pentose Shunt (Pathway, from Glucose-6-phosphate)
Glucose-6-phosphate --> 6-phospho-gluconate --> Ribose 5-phosphate
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Pentose Shunt accomplishes what?
- Anabolic:
- -Generates NADPH for biosynthesis
- Catabolic:
- -Generates pentose-P for nucleotide
- -Degrades pentose from diet
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Pentose Shunt Balanced Reaction
3Glucose-6-P+6NADP++3H2O-->6NADPH+6H++3CO2+2 Fructose-6-P+Glyceraldehyde-3-P
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Two Phases of Phosphate Shunt
- Oxidative: NADPH and Ribose-5-P
- Non-oxidative rearrangements: Fructose-6-P and Glyceraldehyde-3-P
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Pentose Shunt Oxidative Step 1:
Oxidative
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Pentose Shunt Oxidative Reaction 2:
Oxidative
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Pentose Shunt Oxidative Reaction 3
Oxidative
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Pentose Shunt Oxidative Step 4
Oxidative
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Pentose Shunt: Oxidative Overview
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Pentose Shunt Non-oxidative Reaction 1
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Carbon Rearrangements during Non-oxidative phase of Pentose Shunt
- Reaction 2: C5+C5 --> C3+C7 (Transketolase)
- Reaction 3: C7+C3 --> C6+C4 (Transaldolase)
- Reaction 4: C5+C4 --> C6+C3 (Transketolase)
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Pentose Shunt Non-oxidative phase Reaction 2
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Group Transferred during Reaction 2 of Non-oxidative phase of Pentose Shunt
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Pentose Shunt Non-oxidative phase Reaction 3
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Group Transferred in Non-oxidative reaction 3 of Pentose Shunt
- .............CH2---OH
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- C==O
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- HO--C--H
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Pentose Shunt Non-oxidative phase Reaction 4
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Transferred Group in Non-oxidative Step 4 of Pentose Shunt
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Flux of Metabolites in Pentose Shunt
- Nucleotide Biosynthesis: Ribose-5-Phosphate
- NADPH Production: Generation of Fructose-6-phosphate/Glyceraldehyde-3-phosphate
Energy generation: Generation of Fructose-6-phosphate and Glyceraldehyde-3-phospahte for Glycolysis/TCA
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Ribose-5-Phosphate from PP Pathway used in?
Nucleotide Synthesis
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Glyceraldehyde-3-Phosphate/Fructose-6-Phosphate made in PP Pathway used for?
- NADPH Synthesis through Gluconeogenisis into glucose-6-phosphate to repeat cycle
- or:
- Energy generation by going through TCA cycle
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Rate Limiting Step of PP Pathway
Glucose-6-Phosphate Dehydrogenase
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What substrate's availability controls PP Pathway?
NADP+
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Reactive Oxygen Species
- O2 + e- --> O2- (Superoxide)
- O2 + 2e- + 2H+ --> H2O2 (peroxide)
- O2 + 3e- + 3H+ --> H2O + .OH (hydroxyl free radical)
- O2 + 4e- + 4H+ --> 2 H2O
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Negative Outcomes of ROS
- -Mutation in DNA
- -Denatures Proteins
- -Mitochondria produce ROS
- -Mitochondria lack DNA repair
- -Mitochondria susceptible to mutation
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Defenses Against ROS
- Superoxide Dismutase:
- Turns 2 superoxides and 2 protons into Peroxide and O2
- Peroxidase, Catalase:
- Turns 2 peroxides into 2 waters and O2
- Glutathione peroxidase:
- Turns 2GSH + H2O2 --> GSSG +2H20
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Role of NADPH/Glutathione in ROS removal
Glutathione reduces the anti-oxidants to that can neutralize more ROS, then transfers the energy to NADPH so that it is useful
LOOK INTO
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Inherited Glucose-6-P Dehydrogenase Deficiency in Erythrocytes
- Normal circumstances=no symptoms
- Confers resistance to malaria (falciparum)
- Causes oxidative stress towards parasite
- Malaria drugs create oxidative stress in blood
- Divicine (in fava beans) produces oxidative stress.
- Those lacking G-6-P dehy cannot repair,
- can lead to hemolytic anemia
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Wernicke-Korsakoff Syndrome
- -Severe hemolytic anemia
- -Uncoordinated movement, eye movement, amnesia
- -Common in alcoholics
- -Ethanol inhibits thiamine uptake
- -W-K syndrome results in transketolase that does not bind thiamine well
- -Thiamine deficiency inhibits PP Pathway, reduces NADPH
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ROS in Phagocytosis
- NADPH + 2O2 --> NADP+ + 2O2- + H+
- Powerful microbicide
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