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TCA Cycle Krebs Cycle and Citric Acid Cycle Explained

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What Is the TCA Cycle Steps Enzymes and ATP Yield

The series of chemical reactions taking place in cells of all aerobic organisms to release energy which is stored in the form of ATP by conversion of Acetyl CoA derived from carbohydrates, fats, and proteins are defined as the TCA cycle or Tricarboxylic Acid Cycle. It is also known as the Citric Acid cycle and it takes place in mitochondria in the second phase of cellular respiration. Soluble enzymes catalyze the reactions in the TCA cycle.

It is a common anaerobic pathway giving NADH and FADH2. Each of these transfers their electrons to the next pathway bringing about the oxidation. Without the electron, transfer oxidation will not take place. TCA Cycle directly produces less amount of ATP or energy molecules. And it is a cyclic pathway because the last step regenerates the first molecules of the pathway thus making it a closed loop. It occurs in the presence of oxygen.


Why is The TCA Cycle Also Called The Krebs Cycle?

The TCA Cycle or Citric Acid cycle was proposed by British Biochemist Sir Hans Adolf Krebs. Krebs elucidated most of the reactions in this pathway and also received recognition for his work. Furthermore, Fritz Lipmann and Nathan Kaplan discovered Coenzyme A later letting other researchers work out the complete cycle as we know it today.


TCA Cycle

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Steps of TCA Cycle

The TCA cycle is an eight-step pathway that plays a major role in the breakdown of organic molecules. Macromolecules like glucose, sugars, fatty acids, amino acids, etc. cannot directly enter the TCA cycle. Thus, they are first broken down into two-carbon compound Acetyl CoA. After Acetyl CoA enters the TCA cycles, it undergoes other chemical reactions to produce carbon dioxide and energy. Every step of the pathway is catalyzed by a soluble enzyme.


Oxidation of Pyruvate

Pyruvate derived from glucose undergoes oxidation to give acetyl CoA. Acetyl CoA thus enters the cycle and a series of reactions follows


Step 1

Acetyl-CoA which is a two carbon molecules compound, combines with a four-carbon compound, oxaloacetate, resulting in the formation of a six-carbon molecule called citrate and releases the CoA group.


Step 2

In the next step, citrate gets converted into an isomer of citrate called- isocitrate. Two processes simultaneously occur in this step. At first, citrate loses a water molecule and again gains it to form isocitrate.


Step 3

The third step oxidation of isocitrate occurs. A five-carbon molecule called ɑ-ketoglutarate is left behind with the release of a molecule of carbon dioxide is released. NAD+ also gets reduced to NADH. This step is catalyzed by the enzyme isocitrate dehydrogenase.


Step 4

In this step, ɑ-ketoglutarate is oxidized, releasing a molecule of carbon dioxide and reducing NAD+ to NADH. Simultaneously, CoA is picked up by the remaining four-carbon molecules forming Succinyl CoA which is an unstable compound. This step is catalyzed by the enzyme ɑ-ketoglutarate.


Step 5

The phosphate group replaces CoA from succinyl CoA. It then gets transferred to ADP to give rise to the ATP molecule. This step also gives a four-carbon molecule- Succinate.


Step 6

In this step, Succinate is oxidized to give fumarate. Also, two hydrogen atoms are transferred to FAD giving rise to FADH2. FADH2 then transfers its electrons directly to the electron transport chain (ETC) as the enzyme that catalyzes this reaction is embedded in the inner membrane of mitochondria.


Step 7

A water molecule is added to fumarate and fumarate gets converted to malate with the help of enzyme Fumarase.


Step 8

In this step of the cycle, the oxidation of malate regenerates oxaloacetate which is a four-carbon compound, and another molecule of NAD+ is reduced to NADH. This step is catalyzed by the enzyme Malate Dehydrogenase.


End Products of TCA Cycle

One cycle of Citric Acid generates the following end products-

  • Two molecules of carbon dioxide

  • Three molecules of NADH, three hydrogen ions, one molecule of FADH₂

  • One molecule of GTP


To Sum Up The Entire Cycle

Two carbon molecules enter from acetyl CoA in the pathway, and two molecules of carbon dioxide are released. Three molecules of NADH, three hydrogen ions, one molecule of FADH₂ are produced and One molecule of ATP is produced.

It should be noted that one glucose molecule gives rise to two molecules of Acetyl CoA. Thus, the total end products get doubled.


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FAQs on TCA Cycle Krebs Cycle and Citric Acid Cycle Explained

1. What is the TCA cycle?

The TCA cycle (Tricarboxylic Acid cycle) is a central metabolic pathway that oxidizes acetyl-CoA to produce energy in the form of NADH, FADH₂, and ATP (or GTP).

It is also known as the:

  • Krebs cycle
  • Citric acid cycle
It occurs in the mitochondrial matrix of eukaryotic cells and plays a key role in cellular respiration by supplying high-energy electrons to the electron transport chain.

2. Where does the TCA cycle occur in the cell?

The TCA cycle occurs in the mitochondrial matrix of eukaryotic cells.

In different organisms:

  • In eukaryotes, it takes place inside mitochondria.
  • In prokaryotes, it occurs in the cytoplasm because they lack mitochondria.
This location allows the NADH and FADH₂ produced to directly feed into the electron transport chain located on the inner mitochondrial membrane.

3. What is the main function of the TCA cycle?

The main function of the TCA cycle is to generate high-energy electron carriers that drive ATP production.

Its key roles include:

  • Oxidizing acetyl-CoA to CO₂
  • Producing 3 NADH, 1 FADH₂, and 1 GTP (or ATP) per cycle
  • Providing intermediates for biosynthesis (amino acids, nucleotides)
It is therefore both a catabolic and amphibolic pathway.

4. What are the steps of the TCA cycle in order?

The TCA cycle consists of eight enzyme-catalyzed steps that regenerate oxaloacetate.

The main steps are:

  • Formation of citrate from acetyl-CoA and oxaloacetate
  • Conversion of citrate to isocitrate
  • Oxidation to α-ketoglutarate (CO₂ released, NADH formed)
  • Formation of succinyl-CoA (CO₂ released, NADH formed)
  • Conversion to succinate (GTP/ATP produced)
  • Oxidation to fumarate (FADH₂ formed)
  • Conversion to malate
  • Regeneration of oxaloacetate (NADH formed)
This completes one full turn of the cycle.

5. How many ATP are produced in the TCA cycle?

The TCA cycle directly produces 1 ATP (or GTP) per turn, but indirectly generates much more through NADH and FADH₂.

Per one acetyl-CoA, it yields:

  • 3 NADH
  • 1 FADH₂
  • 1 GTP (or ATP)
After oxidative phosphorylation, this equals approximately 10 ATP per acetyl-CoA.

6. Why is the TCA cycle called the citric acid cycle?

The TCA cycle is called the citric acid cycle because the first stable product formed is citrate (citric acid).

During the first step:

  • Acetyl-CoA combines with oxaloacetate
  • This reaction forms citrate, a six-carbon compound
The name reflects this key initial intermediate in the pathway.

7. What is the role of NADH and FADH₂ in the TCA cycle?

In the TCA cycle, NADH and FADH₂ carry high-energy electrons to the electron transport chain for ATP production.

Their roles include:

  • Transporting electrons to the electron transport chain (ETC)
  • Driving oxidative phosphorylation
  • Enabling large-scale ATP synthesis
Without NADH and FADH₂, the majority of ATP from cellular respiration would not be produced.

8. How is the TCA cycle regulated?

The TCA cycle is regulated mainly by energy levels and key regulatory enzymes.

Major control points include:

  • Citrate synthase
  • Isocitrate dehydrogenase
  • α-ketoglutarate dehydrogenase
It is activated by ADP and inhibited by high levels of ATP, NADH, and certain intermediates, ensuring energy balance in the cell.

9. What is the difference between glycolysis and the TCA cycle?

The main difference between glycolysis and the TCA cycle is their location, oxygen dependence, and function in cellular respiration.

Key differences:

  • Location: Glycolysis occurs in the cytoplasm; TCA cycle occurs in the mitochondrial matrix.
  • Oxygen: Glycolysis can occur without oxygen; the TCA cycle is aerobic (indirectly requires oxygen).
  • Function: Glycolysis breaks glucose into pyruvate; the TCA cycle oxidizes acetyl-CoA to CO₂ and produces electron carriers.
Both are interconnected steps in energy metabolism.

10. Why is the TCA cycle considered amphibolic?

The TCA cycle is considered amphibolic because it functions in both catabolism and anabolism.

It is:

  • Catabolic — breaking down acetyl-CoA to release energy.
  • Anabolic — providing intermediates like α-ketoglutarate and oxaloacetate for synthesis of amino acids and other biomolecules.
This dual role makes it a central hub in cellular metabolism.


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