The Krebs Tricarboxylic Acid Cycle - PowerPoint PPT Presentation

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The Krebs Tricarboxylic Acid Cycle

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The Krebs Tricarboxylic Acid Cycle The Final Common Pathway of Oxidative Metabolism 9/24/07 The Three Stages of Metabolism The Krebs Cycle Citric Acid Cycle; The TCA ... – PowerPoint PPT presentation

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Title: The Krebs Tricarboxylic Acid Cycle


1
The Krebs Tricarboxylic Acid Cycle
  • The Final Common Pathway of Oxidative Metabolism
  • 9/24/07

2
? Liver
Gluconeogenesis 1? Liver, Kidney
e- Ox phos
3
Citric Acid Cycle (CAC) Kreb Cycle Tricarboxylic
Acid Cycle
2/3 of O2 consumption needed for oxidation of
Acetyl CoA ? CO2
  • Occurs exclusively in the
  • mitochondrion (matrix)
  • OAA acts as carrier or acceptor
  • of acetyl CoA units is regenerated
  • Burns acetyl CoA to CO2 during
  • this oxidation es from acetyl CoA
  • are trapped in the form of

NADH
Pyruvate Dehydrogenase Complex links glycolysis
to CAC
FADH
2e
2e
2e
2e
4
The Three Stages of Metabolism
5
The Krebs Cycle
  • Citric Acid Cycle The TCA Cycle
  • Pyruvate (actually the acetyl group) from
    glycolysis is degraded to CO2
  • The acetyl group is formed in stage II of
    metabolism from carbohydrate and amino acid
    metabolism
  • 1GTP (ATP in bacteria) and 1 FADH2 is produced
    during one turn of the cycle
  • 3 NADH are produced during one turn of the cycle
  • NADH and FADH2 energize electron transport and
    oxidative phosphorylation
  • Eight reactions make up the Krebs cycle

6
The Chemical Logic of the Krebs Cycle
  • After condensing acetate with oxaloacetate to
    form citrate oxidation yields CO2, oxaloacetate
    is regenerated, and the energy is captured as
    NADH, FADH2, and GTP (ATP)
  • Acetyl-CoA is called the stoichiometric
    substrate it is consumed in large amounts
  • Oxaloacetate is called the regenerating
    substrate it is continuously regenerated (it is
    not consumed)
  • The cycle is catalytic oxaloacetate is consumed
    and then regenerated.

7
Overview of the Krebs Cycle A Mitochondrial
Process
8
Anatomy of the Mitochondrion
  • Which membrane is impermeable to protons and
    other ions?
  • Which membrane will allow for the transport of
    molecules up to a molecular weight of about 1000?

9
Pyruvate Dehydrogenase Complex
Cytoplasm Pyruvate
Multimolecular aggregate
3 Enzymes
5 Coenzymes
5 Reactions
Irreversible
CoA contains the vitamin Pantothenic acid
Links glycolysis to CAC
Product Inhibition
Mitochondrial matrix
NAD
FAD
CoA
Lipoic acid
10
PDH Deficiency results in Congenital Lactic
Acidosis
Pyruvate cannot enter the CAC and results in ?
Lactic Acid
Primarily affects the brain neonatal death
3 Forms psychomotor retardation
v Possible treatment is ketogenic diet
Low in CHO
High in fats
Produces ketone bodies as an alternate form of
energy for the brain
Arsenic Poisoning Pyruvate Dehydrogenase
a-Ketoglutarate Dehydrogenase
Both require lipoic acid as a cofactor
Arsenite Trivalent form of arsenic
I Forms a stable complex with the thiol (-SH)
group of Lipoic Acid
II Glyceraldehyde 3-PO4 step forms complex
with inorganic Pi thus prevents ATP
formation in glycolysis
Affects the brain Death, neurologic problems
11
v Allosteric Regulation
v Allosteric Regulation
12
Aldo condensation
The entrance of acetyl CoA does not ? or ?
intermediates in the CAC
Isomerization
Oxidative decarboxylation
e
Irreversible (1)
One of the rate limiting Rxs of the CAC
ATP
13
Oxidative decarboxylation
Very similar to the Pyruvate Dehydrogenase
complex
Irreversible (2)
e
Substrate Level Phosphorylation
Nucleoside Biphosphate Kinase
e
Oxidation reaction
Hydration reaction
14
Reversible oxidation reaction
15
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16
Main Points of the Krebs Cycle
  • Occurs in mitochondrion
  • All enzymes are hydrophilic and occur in the
    matrix except for succinate dehydrogenase, which
    occurs in the inner mitochondrial membrane
  • Citrate synthase, Isocitrate dehydrogenase and
    a-ketoglutarate dehydrogenase are the three
    irreversible reactions
  • ICD is the main regulatory enzyme, and it is
    activated by ADP
  • Succinate dehydrogenase is inhibited by malonate
    and oxaloacetate

17
Summary
This ratio determines the rate of oxidative
phosphorylation
Named Respiratory Control of energy production
because oxidation and phosphorylation of ADP must
occur simultaneously
18
Electrochemical gradient
19
2 Shuttle systems to bring cytosolic NADH
into mitochondria for oxidative phosphorylation
1) Glycerophosphate shuttle 36 ATP
2) Malate-aspartate shuttle 38 ATP
Count ATPs Anerobic glycolysis 2
Glycolysis CAC oxidative
phosphorylation 38
NADH FADH2 ATP
1 Glycolysis 2
2 Glycolysis (G-3-P ? 1,3,BisP) 2 6
3 Pyruvate ? Acetyl CoA 2 6
4, 5, 6 CAC 6 18
7 CAC-FADH2 2 4
8 CAC substrate level ATP 2
Total 38
20
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