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TCA Cycle

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20 views6 pages

TCA Cycle

Uploaded by

chukwuemekav111
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as DOCX, PDF, TXT or read online on Scribd
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Page 1 of 6

2024

The Tricarboxylic Acid Cycle


Chinonso Emmanuel Dim
Department of Animal Science, University of Nigeria, Nsukka 410001, Enugu
State, Nigeria
E-mail: [email protected]; ORCID: https://orcid.org/0000-0002-7295-
2938

Introduction
Objectives
 To understand the structure and function of the TCA cycle.
 To explore the biochemical steps involved in the cycle.
 To analyze the significance of the TCA cycle in energy production and
metabolic integration.
Expected Outcomes
By the end of this topic, students should be able to:

 Describe each step of the TCA cycle and its associated enzymes.
 Explain how the TCA cycle integrates with other metabolic pathways.
 Discuss the importance of the TCA cycle in cellular respiration and
energy production.
The Tricarboxylic Acid (TCA) cycle, also known as the Krebs cycle or citric
acid cycle, is a crucial metabolic pathway that plays a central role in cellular
respiration. It is involved in the oxidation of acetyl-CoA derived from
carbohydrates, fats, and proteins to produce energy in the form of ATP, as
well as high-energy electron carriers like NADH and FADH₂. Understanding
this cycle is essential for students studying biochemistry, animal science,
and nutrition because it provides insights into how organisms convert food
into usable energy.

Location of the TCA Cycle


The TCA cycle occurs in the mitochondrial matrix of eukaryotic cells.
Mitochondria are often referred to as the "powerhouses" of the cell because
they are responsible for producing ATP through aerobic respiration. The inner
mitochondrial membrane contains various transport proteins that facilitate
the entry of substrates like pyruvate (derived from glycolysis) and fatty acids
into the mitochondria for further processing.

The Tricarboxylic Acid Cycle


Chinonso Emmanuel Dim (RAS)
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2024

Importance of Aerobic Metabolism


The TCA cycle is an aerobic process, meaning it requires oxygen to function
efficiently. Oxygen serves as the final electron acceptor in the electron
transport chain, which is closely linked to the TCA cycle. The ability to utilize
oxygen allows organisms to extract more energy from nutrients compared to
anaerobic processes, making aerobic metabolism a highly efficient means of
energy production.

The TCA Cycle


The cycle consists of a series of enzymatic reactions that convert acetyl-CoA
into carbon dioxide while generating high-energy electron carriers. The cycle
begins with the condensation of acetyl-CoA with oxaloacetate to form citrate
and ends with the regeneration of oxaloacetate, allowing the cycle to
continue.

Key Substrates and Products


 Substrates: Acetyl-CoA, oxaloacetate.
 Products: NADH, FADH₂, ATP (or GTP), CO₂.

Importance of NADH and FADH₂


NADH and FADH₂ generated during the TCA cycle are crucial for ATP
production. They donate electrons to the electron transport chain, where
oxidative phosphorylation occurs. This process results in additional ATP
production through chemiosmosis.

Steps of the TCA Cycle


The TCA cycle consists of eight key steps, each catalyzed by specific
enzymes. Below is a detailed discussion of each step:

Step 1: Formation of Citrate


The cycle begins with acetyl-CoA combining with oxaloacetate to form
citrate. This reaction is catalyzed by citrate synthase.

Reaction:
Acetyl CoA+Oxaloacetate→Citrate+CoAAcetyl CoA+Oxaloaceta
te→Citrate+CoA
Citrate synthase catalyzes this condensation reaction. The enzyme
undergoes conformational changes upon binding acetyl-CoA and

The Tricarboxylic Acid Cycle


Chinonso Emmanuel Dim (RAS)
Page 3 of 6
2024
oxaloacetate, facilitating their interaction. The release of CoA allows it to
participate in other metabolic processes.

Diagram 1: Formation of Citrate

Step 2: Isomerization to Isocitrate


Citrate is then converted into its isomer, isocitrate, through a two-step
process involving dehydration followed by rehydration. The
enzyme aconitase facilitates this reaction.

Reaction:
Citrate⇌IsocitrateCitrate⇌Isocitrate
Aconitase catalyzes this reversible reaction by first removing a water
molecule from citrate to form cis-aconitate and then adding a water
molecule back to form isocitrate. This step prepares citrate for subsequent
oxidative decarboxylation.

Diagram 2: The Isomerization process to Isocitrate

Step 3: Oxidation to α-Ketoglutarate


In this step, isocitrate undergoes oxidative decarboxylation catalyzed
by isocitrate dehydrogenase. A molecule of carbon dioxide is released,
and NAD⁺ is reduced to NADH.

Reaction:
Isocitrate→
Ketoglutarate+CO2+NADHIsocitrate→ Ketoglutarate+CO2
+NADH
Isocitrate dehydrogenase catalyzes a key regulatory step in the TCA cycle. It
has two forms (NAD⁺-dependent and NADP⁺-dependent), but NAD⁺ is
primarily used in mammalian systems. The reaction releases CO₂ and
produces NADH, marking an important point for energy extraction.

Diagram 3: The Oxidation Process to α-Ketoglutarate

Step 4: Decarboxylation to Succinyl-CoA


α-Ketoglutarate undergoes another oxidative decarboxylation catalyzed
by α-ketoglutarate dehydrogenase. A second carbon dioxide molecule is
released while another NAD⁺ is reduced to NADH, forming succinyl-CoA.

The Tricarboxylic Acid Cycle


Chinonso Emmanuel Dim (RAS)
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2024
Reaction:
Ketoglutarate→Succinyl CoA+CO2+NADH Ketoglutarate→Succi
nyl CoA+CO2+NADH
The α-Ketoglutarate dehydrogenase complex functions similarly to pyruvate
dehydrogenase and requires cofactors such as thiamine, lipoic acid, and
coenzyme A for its activity. It represents another critical point for energy
extraction as it produces both NADH and CO₂.

Diagram 4: The Decarboxylation Process to Succinyl-CoA

Step 5: Conversion to Succinate (ATP Production)


Succinyl-CoA is converted into succinate by succinyl-CoA synthetase.
During this process, a phosphate group replaces CoA, which is then
transferred to GDP or ADP to produce GTP or ATP through substrate-level
phosphorylation.

Reaction:
Succinyl CoA+GDP ADP+Pi→Succinate+GTP ATP+CoASuccinyl C
oA+GDP ADP+Pi→Succinate+GTP ATP+CoA
The succinyl-CoA synthetase catalyzes substrate-level phosphorylation
where GTP or ATP is produced directly from succinyl-CoA without involving
oxidative phosphorylation.

Diagram 5: The Conversion Process to Succinate

Step 6: Oxidation of Succinate to Fumarate


Succinate is oxidized to fumarate by succinate dehydrogenase, reducing
FAD to FADH₂.

Reaction:
Succinate→Fumarate+FADH2Succinate→Fumarate+FADH2
The succinate dehydrogenase enzyme is unique as it resides within the inner
mitochondrial membrane and directly links the TCA cycle with the electron
transport chain (ETC). The FADH₂ produced here will later contribute
electrons for ATP synthesis via oxidative phosphorylation.

Diagram 6: The Oxidation of Succinate

The Tricarboxylic Acid Cycle


Chinonso Emmanuel Dim (RAS)
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2024

Step 7: Hydration of Fumarate to Malate


Fumarate undergoes hydration (addition of water) catalyzed by fumarase to
form malate.

Reaction:
Fumarate+H2O→MalateFumarate+H2O→Malate
Fumarase catalyzes this reversible hydration reaction without producing any
high-energy molecules; however, it prepares malate for oxidation in the final
step.

Diagram 7: The Hydration of Fumarate

Step 8: Regeneration of Oxaloacetate


In this final step, malate is oxidized back to oxaloacetate by malate
dehydrogenase, with another NAD⁺ being reduced to NADH.

Reaction:
Malate→Oxaloacetate+NADHMalate→Oxaloacetate+NADH
Malate dehydrogenase catalyzes this oxidation reaction while regenerating
oxaloacetate for another turn of the cycle; it also produces another molecule
of NADH that will contribute further electrons for ATP production via oxidative
phosphorylation.

Diagram 8: The Regeneration of Oxaloacetate

End Products of the TCA Cycle


Each complete turn of the TCA cycle yields:

 3 NADH
 1 FADH₂
 1 GTP (or ATP)
 2 CO₂
These products play vital roles in cellular metabolism:
 NADH and FADH₂: Serve as electron carriers that feed into the
electron transport chain.
 GTP or ATP: Provides immediate energy for cellular functions.
 CO₂: A waste product of cellular respiration.

The Tricarboxylic Acid Cycle


Chinonso Emmanuel Dim (RAS)
Page 6 of 6
2024

Significance of the TCA Cycle


Energy Production
The TCA cycle plays a crucial role in generating high-energy molecules that
are essential for ATP synthesis through oxidative phosphorylation in
mitochondria:

Electron Transport Chain:


 NADH and FADH₂ produced during the TCA cycle donate
electrons.
 This process creates a proton gradient across mitochondrial
membranes leading to ATP synthesis via ATP synthase.
 Each NADH can yield approximately 2.5 ATPs while each FADH₂
can yield about 1.5 ATPs when processed through oxidative
phosphorylation.

Metabolic Pathway Integration


The TCA cycle serves as a central hub connecting various metabolic
pathways:

1. Carbohydrate Metabolism:
 Pyruvate from glycolysis enters as acetyl-CoA.
2. Fatty Acid Oxidation:
 Fatty acids are broken down into acetyl-CoA units that enter
directly into the TCA cycle.
3. Amino Acid Catabolism:
 Certain amino acids can be converted into intermediates that
feed into different points within the TCA cycle.
4. Anaplerotic Reactions:
 Reactions that replenish intermediates consumed during
biosynthesis ensure continuous operation even under varying
metabolic demands.

The Tricarboxylic Acid Cycle


Chinonso Emmanuel Dim (RAS)

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