The Citric Acid Cycle

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The Citric Acid Cycle

• TCA Cycle (Tricarboxylic Acid Cycle)
• and the Krebs Cycle

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Respiration

• Typically referred to as the physiological uptake
  of O2 and the release of CO2
• Biochemists and Cell Biologists refer to cellular
  respiration as the consumption of O2 in molecular
  processes and the production of CO2

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Acetyl-CoA

• The entry point to the TCA cycle from pyruvate,
  glycolysis.
• Produced from pyruvate by the pyruvate
  dehydrogenase complex, PDH

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The PDH Complex

• Consists of three different enzymes, pyruvate
  dehydrogenase (E1), dyhydrolipoyl transacetylase
  (E2), and dyhyrolipoyl dehydrogenase (E3)
• and
• Five different coenzymes or prosthetic groups

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An example of Substrate Channeling
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Takes place in the mitochondrion.
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aconitase, or aconitate hydratase
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The Iron-Sulfur center of aconitase
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This enzyme closely resembles PDH discussed
previously
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This enzyme is tightly bound to the inner
membrane of the mitochondrion in eukaryotes,
plasma membrane in prokaryotes. It has three
iron-sulfur clusters and an FAD molecule.
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Fumarase

• Highly stereospecific
• Will only bind and catalyze the trans double bond
  of fumarate not maleate, the cis isomer of
  fumarate.
• Will only bind and catalyze the dehydration of
  L-malate not D-malate

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Products of one turn of the cycle, the net yield
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Anaerobic Bacteria lack a-ketoglutarate dehydrogen
ase. They cannot carry out the complete TCA
cycle but the intermediates are needed in
other processes.
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TCA cycle intermediates are used in other
processes, but are replaced in other steps
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Regulation through the TCA cycle

• The TCA cycle is regulated mainly in its three
  irreversible steps, and in the leading step
  catalyzed by the PDH complex.

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Regulation through the TCA cycle complex, yet is
designed to coordinate with glycolysis and other
processes in the cell.
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The Glyoxylate Cycle

• Vertebrates can not convert fatty acids or their
  catabolic products into carbohydrates.
• Acetyl-CoA cannot be converted to glucose
• We might think
• oxaloacetate GTP ? PEP CO2 GDP

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Every entry of an acetyl group results in the
loss of two CO2 molecules in the cycle.
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The Glyoxylate Cycle

• Some organisms, plants, some invertebrates and
  some microbes have the enzymes necessary to carry
  out the glyoxylate cycle.
• Isocitrate lyase
• Malate synthase

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The Glyoxylate Cycle

• In plants takes place in glyoxysomes,
  specialized peroxisomes.

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The processes take place in their own
separate compartment but with free exchange of
intermediates between the compartments the
processes are easily controlled and coordinated.
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The regulation of the two processes
are coordinated.