Page 1
Discipline: Botany
Paper: Plant Metabolism
Lesson: Pyruvate metabolism in Mitochondria and
Tricarboxylic Acid Cycle
Lesson Developer: Dr. Manju A. Lal
Department of Botany,
Kirori Mal College, University of Delhi
Page 2
Discipline: Botany
Paper: Plant Metabolism
Lesson: Pyruvate metabolism in Mitochondria and
Tricarboxylic Acid Cycle
Lesson Developer: Dr. Manju A. Lal
Department of Botany,
Kirori Mal College, University of Delhi
Pyruvate metabolism in mitochondria and Tricarboxylic Acid Cycle
Institute o f Lifelong Learning, University of Delhi, 2
Table of contents
? Introduction
? Oxidative decarboxylation of pyruvate
? Enzymes and cofactors involved
? Pyruvate dehydrogenase complex (PDH)
? Mechanism of the reaction
? Regulation of the enzyme activity
? Tricarboxylic acid cycle
? Discovery of the cycle
? Enzymes and the pathway
? Carbon balance of the cycle
? Energetics of the cycle
? Amphibolic role of the cycle
? Role of TCA cycle in anabolism
? Role of TCA cycle in catabolism
? Anaplerotic reactions
? Regulation of TCA cycle
? Unique features of TCA cycle in plants
? Summary
? Exercises
? Glossary
? References
? Web links
Page 3
Discipline: Botany
Paper: Plant Metabolism
Lesson: Pyruvate metabolism in Mitochondria and
Tricarboxylic Acid Cycle
Lesson Developer: Dr. Manju A. Lal
Department of Botany,
Kirori Mal College, University of Delhi
Pyruvate metabolism in mitochondria and Tricarboxylic Acid Cycle
Institute o f Lifelong Learning, University of Delhi, 2
Table of contents
? Introduction
? Oxidative decarboxylation of pyruvate
? Enzymes and cofactors involved
? Pyruvate dehydrogenase complex (PDH)
? Mechanism of the reaction
? Regulation of the enzyme activity
? Tricarboxylic acid cycle
? Discovery of the cycle
? Enzymes and the pathway
? Carbon balance of the cycle
? Energetics of the cycle
? Amphibolic role of the cycle
? Role of TCA cycle in anabolism
? Role of TCA cycle in catabolism
? Anaplerotic reactions
? Regulation of TCA cycle
? Unique features of TCA cycle in plants
? Summary
? Exercises
? Glossary
? References
? Web links
Pyruvate metabolism in mitochondria and Tricarboxylic Acid Cycle
Institute o f Lifelong Learning, University of Delhi, 3
Learning outcomes
In this lesson you will learn about:
1. Pyruvate metabolism in the mitochondria by oxidative decarboxylation. You will
learn about the steps of the reactions, the enzymes and cofactors involved and also
about the regulation of the enzymes.
2. Tricarbxylic acid cycle: the acetyl-Coenzyme A, which is produced in the above said
reaction, enters TCA cycle. You will learn about the discovery of the cycle, reactions
of the cycle, the enzymes and regulation of the cycle.
3. Anabolic and catabolic roles of the TCA cycle.
4. ‘Filling up’ pathways, which are responsible for replenishing the intermediates of the
cycle.
Introduction
In the previous lesson you have studied that glucose is converted to pyruvate in the
cytosol by a metabolic process known as glycolysis. There is no requirement of oxygen in
the glycolytic process. However, further fate of pyruvate is determined by the availability
of oxygen. In case oxygen is not available, pyruvate is either converted to lactic acid or
ethyl alcohol by the fermentation process in the cytosol itself. However, in presence of
oxygen, glycolytic NADH is oxidized by the electron transport chain (located in the inner
mitochondrial membrane), and pyruvate is transported to mitochondria for further
metabolism. Because of the presence of porins, the outer membrane of mitochondria is
freely permeable to many solutes (having the size up to 10,000 daltons) but not to
proteins. The inner mitochondrial membrane has restricted permeability. There are
transporters present in the inner mitochondrial membrane, which allow the passage of
selective molecules across the membrane, so that the compartmentalization of the
chemical environment inside the mitochondria can be regulated, and the optimal
requirement for various metabolic reactions, occurring inside the organelle, can be
maintained. Pyruvate translocator, present in the inner mitochondrial membrane,
transports pyruvate inside the mitochondria from the cytosol in exchange of OH- ions.
Page 4
Discipline: Botany
Paper: Plant Metabolism
Lesson: Pyruvate metabolism in Mitochondria and
Tricarboxylic Acid Cycle
Lesson Developer: Dr. Manju A. Lal
Department of Botany,
Kirori Mal College, University of Delhi
Pyruvate metabolism in mitochondria and Tricarboxylic Acid Cycle
Institute o f Lifelong Learning, University of Delhi, 2
Table of contents
? Introduction
? Oxidative decarboxylation of pyruvate
? Enzymes and cofactors involved
? Pyruvate dehydrogenase complex (PDH)
? Mechanism of the reaction
? Regulation of the enzyme activity
? Tricarboxylic acid cycle
? Discovery of the cycle
? Enzymes and the pathway
? Carbon balance of the cycle
? Energetics of the cycle
? Amphibolic role of the cycle
? Role of TCA cycle in anabolism
? Role of TCA cycle in catabolism
? Anaplerotic reactions
? Regulation of TCA cycle
? Unique features of TCA cycle in plants
? Summary
? Exercises
? Glossary
? References
? Web links
Pyruvate metabolism in mitochondria and Tricarboxylic Acid Cycle
Institute o f Lifelong Learning, University of Delhi, 3
Learning outcomes
In this lesson you will learn about:
1. Pyruvate metabolism in the mitochondria by oxidative decarboxylation. You will
learn about the steps of the reactions, the enzymes and cofactors involved and also
about the regulation of the enzymes.
2. Tricarbxylic acid cycle: the acetyl-Coenzyme A, which is produced in the above said
reaction, enters TCA cycle. You will learn about the discovery of the cycle, reactions
of the cycle, the enzymes and regulation of the cycle.
3. Anabolic and catabolic roles of the TCA cycle.
4. ‘Filling up’ pathways, which are responsible for replenishing the intermediates of the
cycle.
Introduction
In the previous lesson you have studied that glucose is converted to pyruvate in the
cytosol by a metabolic process known as glycolysis. There is no requirement of oxygen in
the glycolytic process. However, further fate of pyruvate is determined by the availability
of oxygen. In case oxygen is not available, pyruvate is either converted to lactic acid or
ethyl alcohol by the fermentation process in the cytosol itself. However, in presence of
oxygen, glycolytic NADH is oxidized by the electron transport chain (located in the inner
mitochondrial membrane), and pyruvate is transported to mitochondria for further
metabolism. Because of the presence of porins, the outer membrane of mitochondria is
freely permeable to many solutes (having the size up to 10,000 daltons) but not to
proteins. The inner mitochondrial membrane has restricted permeability. There are
transporters present in the inner mitochondrial membrane, which allow the passage of
selective molecules across the membrane, so that the compartmentalization of the
chemical environment inside the mitochondria can be regulated, and the optimal
requirement for various metabolic reactions, occurring inside the organelle, can be
maintained. Pyruvate translocator, present in the inner mitochondrial membrane,
transports pyruvate inside the mitochondria from the cytosol in exchange of OH- ions.
Pyruvate metabolism in mitochondria and Tricarboxylic Acid Cycle
Institute o f Lifelong Learning, University of Delhi, 4
Figure: Pyruvate is transported into mitochondria where further metabolism takes place.
Source:http://cnx.org/contents/db89c8f8-a27c-4685-ad2a-
19d11a2a7e2e@13.11:66/Principles_of_Biology (cc)
Oxidative decarboxylation of pyruvate
In mitochondria, pyruvate is converted to acetyl- Coenzyme A by a reaction known as
oxidative decarboxylation, since the terminal carboxylic group of pyruvate is lost as
carbon-dioxide (decarboxylation) and oxidation of pyruvate also occurs, which is coupled
to reduction of NAD
+
to NADH. The reaction can be written as:
Pyruvate dehydrogenase complex
CH
3
COCOO-+ CoA- SH + NAD
+
---------------- ?CH
3
COCoA
+ CO
2
+ NADH
Page 5
Discipline: Botany
Paper: Plant Metabolism
Lesson: Pyruvate metabolism in Mitochondria and
Tricarboxylic Acid Cycle
Lesson Developer: Dr. Manju A. Lal
Department of Botany,
Kirori Mal College, University of Delhi
Pyruvate metabolism in mitochondria and Tricarboxylic Acid Cycle
Institute o f Lifelong Learning, University of Delhi, 2
Table of contents
? Introduction
? Oxidative decarboxylation of pyruvate
? Enzymes and cofactors involved
? Pyruvate dehydrogenase complex (PDH)
? Mechanism of the reaction
? Regulation of the enzyme activity
? Tricarboxylic acid cycle
? Discovery of the cycle
? Enzymes and the pathway
? Carbon balance of the cycle
? Energetics of the cycle
? Amphibolic role of the cycle
? Role of TCA cycle in anabolism
? Role of TCA cycle in catabolism
? Anaplerotic reactions
? Regulation of TCA cycle
? Unique features of TCA cycle in plants
? Summary
? Exercises
? Glossary
? References
? Web links
Pyruvate metabolism in mitochondria and Tricarboxylic Acid Cycle
Institute o f Lifelong Learning, University of Delhi, 3
Learning outcomes
In this lesson you will learn about:
1. Pyruvate metabolism in the mitochondria by oxidative decarboxylation. You will
learn about the steps of the reactions, the enzymes and cofactors involved and also
about the regulation of the enzymes.
2. Tricarbxylic acid cycle: the acetyl-Coenzyme A, which is produced in the above said
reaction, enters TCA cycle. You will learn about the discovery of the cycle, reactions
of the cycle, the enzymes and regulation of the cycle.
3. Anabolic and catabolic roles of the TCA cycle.
4. ‘Filling up’ pathways, which are responsible for replenishing the intermediates of the
cycle.
Introduction
In the previous lesson you have studied that glucose is converted to pyruvate in the
cytosol by a metabolic process known as glycolysis. There is no requirement of oxygen in
the glycolytic process. However, further fate of pyruvate is determined by the availability
of oxygen. In case oxygen is not available, pyruvate is either converted to lactic acid or
ethyl alcohol by the fermentation process in the cytosol itself. However, in presence of
oxygen, glycolytic NADH is oxidized by the electron transport chain (located in the inner
mitochondrial membrane), and pyruvate is transported to mitochondria for further
metabolism. Because of the presence of porins, the outer membrane of mitochondria is
freely permeable to many solutes (having the size up to 10,000 daltons) but not to
proteins. The inner mitochondrial membrane has restricted permeability. There are
transporters present in the inner mitochondrial membrane, which allow the passage of
selective molecules across the membrane, so that the compartmentalization of the
chemical environment inside the mitochondria can be regulated, and the optimal
requirement for various metabolic reactions, occurring inside the organelle, can be
maintained. Pyruvate translocator, present in the inner mitochondrial membrane,
transports pyruvate inside the mitochondria from the cytosol in exchange of OH- ions.
Pyruvate metabolism in mitochondria and Tricarboxylic Acid Cycle
Institute o f Lifelong Learning, University of Delhi, 4
Figure: Pyruvate is transported into mitochondria where further metabolism takes place.
Source:http://cnx.org/contents/db89c8f8-a27c-4685-ad2a-
19d11a2a7e2e@13.11:66/Principles_of_Biology (cc)
Oxidative decarboxylation of pyruvate
In mitochondria, pyruvate is converted to acetyl- Coenzyme A by a reaction known as
oxidative decarboxylation, since the terminal carboxylic group of pyruvate is lost as
carbon-dioxide (decarboxylation) and oxidation of pyruvate also occurs, which is coupled
to reduction of NAD
+
to NADH. The reaction can be written as:
Pyruvate dehydrogenase complex
CH
3
COCOO-+ CoA- SH + NAD
+
---------------- ?CH
3
COCoA
+ CO
2
+ NADH
Pyruvate metabolism in mitochondria and Tricarboxylic Acid Cycle
Institute o f Lifelong Learning, University of Delhi, 5
It is an exergonic reaction with a net standard free energy change of -33.4 kJ mole
-1
(?G
0
’ = - 33.4 kJmole
-1
). The reaction occurs in mitochondrial matrix.
Figure: The step of conversion of pyruvate molecule into acetyl coenzyme A is the
junction between glycolysis and the TCA cycle. It is accomplished by a multi-enzyme
complex that catalyzes three reactions: 1. Pyruvate is oxidized and carboxyl group
(COO–) is removed to release CO
2
. 2. The remaining two-carbon compound is oxidized
and an acetate compound is formed. An enzyme transfers the extracted electrons to
NAD+, storing energy in the form of NADH. 3. Coenzyme A (CoA) is attached to the
acetate by an unstable bond and this makes the acetyl group become very reactive.
Acetyl CoA has a high potential energy will undergoes the TCA cycle to release energy to
make ATP.
Source:http://en.wikibooks.org/wiki/Structural_Biochemistry/Pyruvate_Dehydrogenase_
Complex (cc)
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