Chapter 9: Outline

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Chapter 9 Outline

• OxidatonReduction Reactions
• Citric Acid Cycle
• Pyruvate to Acetyl-CoA
• Reactions of the Citric Acid Cycle
• Fate of Carbons in the Citric Acid Cycle
• Amphibolic Nature of the Cycle
• Regulation of the Citric Acid Cycle
• The Glyoxylate Cycle

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Introduction

• Facultative anerobes and obligate aerobes use
  oxygen to generate energy.
• The oxidation uses the citric acid cycle, the
  electron transport chain, and oxidative
  phosphorylation to pass electrons to dioxygen via
  NADH and FADH2.
• In eukaryotic cells, oxidation occurs in the
  mitochondria.

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9.1 Oxidation-Reduction

• Oxidation occurs when a substance loses
  electrons reduction when a substance gains
  electrons. Eg.
• Cu(aq) Fe3(aq)? Cu2(aq) Fe2(aq)
• Cu oxidized Cu ? Cu2 1e-
• copper loses an electron
• Fe reduced Fe3 1e- ? Fe2
• iron gains an electron

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Oxidation-Reduction-2

• The tendency for a species to gain electrons is
  its reduction potential.
• Standard reduction potentials are measured in an
  electrochemical cell vs a standard hydrogen
  electrode where H2 is 1 atm and H 1.0 M.
• The measured voltage for the Cu/Fe3 couple is
  0.61 volts. (Next slide.)

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Oxidation-Reduction-4

• The standard reduction potential for hydrogen
  under physiological conditions is 0.42 v.
• Electrons flow spontaneously from a species with
  a more negative E0 value to a species with a
  more positive E0 value.

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Oxidation-Reduction-5
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Oxidation-Reduction 6

• Biological oxidation of carbohydrates supplies
  the body with its major energy needs.
• The electrons lost are eventually transferred to
  dioxygen (O2) to produce water.
• Biologically, oxidation is usually the addition
  of oxygen or the removal of two hydrogen from a
  molecule. Reduction is the reverse.

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Oxidation-Reduction 7

• An example of a biological redox system

NADH is reducing agent
pyruvate is reduced
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Pyruvate Decarboxylate Complex
pyruvate
Acetyl CoA
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Decarboxylation
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PDC Continue
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PDC The Multienzyme Complex

• The pyruvate dehydrogenase complex is probably
  arranged in a compact cubic arrangement with each
  enzyme present as dimeric or trimeric complexes.
• The lipoic acid is covalently attached to the
  transacetylase enzyme via a lysine residue. The
  acid and the lysine act as a swinging arm which
  moves to the site of the reactions. (Next slide)

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PDC The Swinging Arm
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9.2 The Citric Acid Cycle

• Acetyl CoA and oxaloacetate feed the citric acid
  (TCA) cycle.
• The acetyl group is oxidized to two molecules of
  CO2 and high energy electrons are transferred to
  NAD and FAD.

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TCA Cycle
Now Recycle and ATP Produced
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The TCA Cycle-1
H2O
Citrate
Oxaloacetate
CoA-SH H
Citrate synthase
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The TCA Cycle-2
Citrate
Isocitrate
aconitase
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The TCA Cycle-3
NAD NADH H
Mg2
CO2
H
a-ketoglutarate
Isocitrate
isocitrate dehydrogenase
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The TCA Cycle-4
CoA-SH
CO2
NAD NADH H
Succinyl-CoA
a-ketoglutarate
a-ketoglutarate dehydrogenase complex
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The TCA Cycle-5
CoA-SH
GTP
GDP
Pi
Succinate
Succinyl-CoA
succinyl-CoA synthetase
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The TCA Cycle-6
FAD
FADH2
Fumarate
Succinate
succinate dehydrogenase
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The TCA Cycle-7
H2O
Fumarate
L-Malate
fumarase
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The TCA Cycle-8
NAD NADH H
Oxaloacetate
L-Malate
malate dehydrogenase
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The Cycle is Amphibolic
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Regulation of the Cycle-1

• Citrate synthase
• Inhibited by citrate, NADH, ATP, and
  succinyl-CoA
• Isocitrate dehydrogenase
• Inhibited by NADH, ATP
• Stimulated by NAD and ADP
• a-ketoglutarate dehydrogenase
• Inhibited by NADH, succinyl-CoA
• Stimulated by NAD and ADP

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Regulation of the Cycle-2

• Pyruvate dehydrogenase and pyruvate carboxylase
  outside the cycle are important in regulation.
• If, for example, oxaloacetate concentration falls
  (eg. a-ketoglutarate used in synthesis), Ac-CoA
  accumulates and this activates pyruvate
  carboxylase and inhibits pyruvate dehydrogenase.

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The Glyoxylate Cycle-1

• Plants and some fungi, algae, protozoans, and
  bacteria can use two-carbon compounds for growth.
• (ethanol, acetate, acetyl-CoA)
• In plants the reaction occurs in the glyoxysomes.
• There are five reaction in the glyoxylate cycle.
  The first two (synthesis of citrate and
  isocitrate) are the same as with the TCA cycle
  but with new enzymes.

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The Glyoxylate Cycle-2

• Two molecules of Ac-CoA are used in the cycle.