1 The matrix contains Pyruvate Dehydrogenase, enzymes of Krebs Cycle, and other pathways, e.g., fatty acid oxidation & amino acid metabolism. matrix inner membrane outer membrane inter- membrane space mitochondrion cristae Glycolysis occurs in the cytosol of cells. Pyruvate enters the mitochondrion to be metabolized further. Mitochondrial Compartments: CH 5. Citric acid cycle
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The matrix contains Pyruvate Dehydrogenase, enzymes of Krebs Cycle, and other pathways, e.g., fatty acid oxidation & amino acid metabolism.
matrix
inner membrane
outer membrane
inter- membrane
space
mitochondrion
cristae
Glycolysis occurs in
the cytosol of cells.
Pyruvate enters the
mitochondrion to be
metabolized further.
Mitochondrial
Compartments:
CH 5. Citric acid cycle
2
Citric acid cycle
Krebs cycle, tricarboxylic acid cycle TCA
The central function is the oxidation of acetyl CoA to CO2
- It is the final common pathway for oxidation of fuel
molecules
- Acetyl CoA is derived from the metabolism of fuel molecules
as amino acids, fatty acids, and carbohydrates.
- Citric acid cycle is also an important source of precursors
Some intermediates are precursors of amino acid
One of the intermediates is used
in the synthesis of porphorins
Another is used in the
synthesis of fatty acids and sterols.
- Citric Acid Cycle located in
the mitochondrial matrix
CH 5. Citric acid cycle
3 CH 5. Citric acid cycle
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Citric acid cycle is also an important source of precursors for biosynthetic reactions
CH 5. Citric acid cycle
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Citric acid cycle intermediates are always in flux
CH 5. Citric acid cycle
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3NAD+ + FAD + GDP + Pi + 2H2O + acetyl-CoA
3NADH + FADH2 + GTP + CoA + 2CO2 + 3H+
Overall reaction
- Citric acid cycle contains a series of oxidation-reduction
reactions
- Carbon entering the cycle, leaves fully oxidized as CO2.
- “High energy” electrons leave the cycle with high energy
electron carriers as NADH and FADH2.
- Very little ATP is made directly in the cycle.
- No oxygen is used in the cycle.
The Citric acid cycle
CH 5. Citric acid cycle
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The citric acid cycle oxidizes two carbon
units. These enter the cycle as Acetyl-CoA
CH 5. Citric acid cycle
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Oxidative Decarboxylation of Pyruvate
- Pyruvate Dehydrogenase complex is a large multi-subunit complex located in
the mitochondria
- Irreversible reaction; Acetyl CoA cannot converted into pyruvate
- Pyruvate dehydrogenase is not a part of citric acid cycle but it a major
source of fuel for citric acid cycle which is Acetyl CoA
- Pyruvate Dehydrogenase complex is aggregate of three enzymes:
1- Pyruvate dehydrogenase component called (pyruvate decarboxylase)
2- Dihydrolipoyl transacetylase
3- Dihydrolipoyl dehydrogenase
Each subunit of this large complex catalyzes a part of the overall reactions. CH 5. Citric acid cycle
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Pyruvate
Dehydrogenase: a large
complex containing many
copies of each of 3
enzymes, E1, E2, & E3.
Enzyme Abbreviated Prosthetic Group
Pyruvate
Dehydrogenase E1
Thiamine
pyrophosphate (TPP)
Dihydrolipoyl
Transacetylase E2
Lipoamide
Dihydrolipoyl
Dehydrogenase E3
FAD
Pyruvate Dehydrogenase Subunits
CH 5. Citric acid cycle
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Cofactors for the
Pyruvate
Dehydrogenase include
CoA-SH, NAD+, TPP,
FAD, Lipolate
CH 5. Citric acid cycle
11 CH 5. Citric acid cycle
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Regulation Pyruvate Dehydrogenase complex
-Product inhibition
-The enzyme complex is inhibited by Acetyl CoA when it is
accumulated; the production rate is higher than the cell
capacity of oxidation with citric acid cycle
- High NADH/NAD+ ratio inhibits this enzyme complex
Covalent modification
-Two forms of the enzyme complex;
- Active non- phosphorylated form
- Inactive phosphorylated form
-The two forms can be interconverted by the action of two enzymes
phosphatase and kinase
- The kinase is activated by an increase in the ratio of acetyl CoA/
CoA ratio or NADH/ NAD+.
- elevated ADP\ATP ratio demand for energy inhibits the
kinase and activate the phosphatase to produce more of the active