The Citric Acid Cycle (Tricarboxylic Acid Cyle)

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The Citric Acid Cycle (Tricarboxylic Acid Cyle)
1. The link between gycolysis and citric acid
cycle 2. TCA cycle oxidizes 2 C units 3.
Entry and metabolism controlled 4. Source of
precursors 5. Glyoxylate cycle enables plants
and bacteria to grow on acetate
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Glucose Metabolism Under Aerobic and Anaerobic
Conditions
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Citric Acid Cycle takes place in the Matrix of
the Mitochondria (Eukaryotic cells, under aerobic
conditions)
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Citric Acid Cycle is the first step in Cellular
Respiration
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The link between Glycolysis and Citric Acid Cycle
Pyruvate dehydrogenase complex (E. coli)
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The conversion from Pyruvate -gt Acetyl-CoA
-gt goes in 3 steps

• And requires
• The 3 enzymes of the complex
• 5 co-enzymes (thiamine pyrophosphate TPP, lipoic
  acid, FAD, CoA, and NAD

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Reaction mechanism of the conversion Pyruvate -gt
Acetyl-CoA
Carbanion of TPP
Reduced form
Oxidized form
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Reaction mechanism of the conversion Pyruvate -gt
Acetyl-CoA
Reduced form
2e-
Oxidized form
Reduced form
Oxidation
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Pyruvate dehydrogenase complex
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The Citric Acid Cycle
Isomerization
Oxidation Decaroboxylation
Generation of electrons
Oxidation (Regeneration of Oxaloacetate)
Oxidative Decarboxylation
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1. Citric Synthase forms citrate from
oxaloacetate and acetyl-CoA
Aldol Condensation
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2. Citrate is isomerized into Isocitrate
Hydroxy group is not located correct for
decarboxylation reaction -gt Isomerization
Aconitase
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3. Isocitrate is Oxidized and Decarboxylated to
a-Ketoglutarate
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4. Oxidative Decarboxylation of a-Ketoglutarate
gives Succinyl-CoA
Mechanism analog to decarboxylation of pyruvate
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5. GTP is generated from Succinyl-CoA
Energy-rich thioester
Synthetase
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6. Oxaloacetate is regenerated by Oxidation of
Succinate

• This metabolic motif -gt also found in
• fatty acid Synthesis degradation,
• degradation of some AA
• Methylene group (CH2) -gt carbonyl group (CO)
• Oxidation
• Hydration
• Oxidation

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3 NADH -gt 6e- 1 FADH2 -gt 2e- --------------- -----
---gt 8e-
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Regulation of the Pyruvate dehydrogenase complex
Regulation by Allosterie Phosphorylation
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Regulation of the Pyruvate dehydrogenase complex
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Control of the Citric Acid Cycle
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The Citric Acid Cycle is a Source of Precursors
Fast refill of oxaloacate by carboxylation of
pyruvate (in mammals)
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Pathway Integration
Pathways active during exercise after a nights
rest
Rate of citric acid cycle increases during
exercise -gt requiring the refill of
oxaloacetate acetyl CoA Oxaloacetate -gt from
pyruvate Acetyl CoA -gt from pyruvate fatty
acids
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Blocking of Pyruvate -gt Acetyl-CoA Reaction
Relieves the inhibition -gt forms complex -gt
excreted
By Poisoning with Hg and As
By Vitamin B1 (thiamine) deficiency Beriberi
TPP (thiamine) is co-factor in reaction
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The Glyoxylate Cycle

• Enables Plant and Bacteria to grow on Acetate
• It bypasses the decarboxylation steps of citric
  acid cycle
• Enzymes that allow conversion from acetate into
  succinate are in blue boxes
• Intake of 2 acetyl groups/cycle
• production of succinate -gt glucose
• regeneration of oxaloacetate from glyoxylate

Plant cell
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Regulation of the glyoxylate cycle