Krebs cycle: definitions, features and stages

Krebs cycle

Introduction

Body constantly needs the energy to control various biological functions. The organism consumes food to gain this energy. The static energy in food that is stored from solar energy through the process of photosynthesis is converted into kinetic energy through a biochemical process of respiration. The organism performs physiological functions such as food intake, growth, movement, excretion, reproduction, etc. by this kinetic energy. The main purpose of respiration is to generate the energy necessary for the body to perform various physiological functions. Respiration is a biochemical process that takes place day and night in the body cells of all living things. Respiration is divided into two types, such as aerobic respiration and anaerobic respiration. Krebs cycle is a phase of this aerobic respiration (1).

Definition of Krebs cycle

It is the third stage of aerobic respiration and is the final common pathway of oxidation of carbohydrates, proteins, and fats through acetyl CoA. In which they are completely oxidized to carbon dioxide and water. In the second stage of aerobic respiration, acetyl CoA derived from pyruvic acid enters the mitochondria, which produces a variety of organic acid, carbon dioxide, and water through a cyclical process called the Krebs cycle. There are no direct roles of oxygen observed in any phase of this cycle, but the cycle is not complete without the presence of oxygen (1) & (3).

Features of Krebs cycle

There are some essential features such as

  • It is an important metabolic pathway.
  • This cycle supplies about 60 to 70% of the energy (ATP) to the body.
  • Carbon dioxide is released during this process.
  • Occurs in aerobic respiration only. That is oxygen as the terminal oxidant.
  • It involves the complete oxidation of pyruvate in carbon dioxide and water.
  • The process starts with the acetyl CoA and oxaloacetate.
  • It is not a linear but cyclical pathway.
  • In this, the oxaloacetate is a normal component of cells. It reacts with acetyl-CoA and water to form citrate (1) & (2).

Who proposed Krebs cycle?

In 1937, scientist Hans Adolf Krebs first proposed the Krebs cycle. He discovered this cycle based on the studies of oxygen consumption in pigeon breast mussels. He was the first to observe this cycle of reactions, hence the cycle is named in his name (4).

Location of Krebs cycle

The Krebs cycle was first noticed in the pigeon’s muscle by scientist Hans Adolf Krebs. This cycle is located in all eukaryotic and prokaryotic cells. It occurs in the chloroplast of the plant cell. The mitochondria of the eukaryotic cell are the main place. And in prokaryotic cells, it occurs in the cytoplasm (1) & (4).

Why is the Krebs cycle called the citric acid cycle?

It is a process that involves the oxidation of acetyl CoA to carbon dioxide and water. At the beginning of the Krebs cycle, the acetyl CoA molecule reacts with a compound called oxaloacetate and produces citric acid or citrate compounds. That is why the Krebs cycle is known as the citric acid cycle (3).

Krebs cycle- an open cycle

Carbohydrates, fatty acids, and amino acids are oxidized by the Krebs cycle. This cycle is not linear in type but is a circle in type which is not a closed circle. Some compounds enter the Krebs cycle and some compounds are released. The Krebs cycle is compared to a national highway with heavy traffic. Just as many roads meet on a national highway, so do various compounds enter in the Krebs cycle. Some compounds also reduce from the Krebs cycle. So the Krebs cycle is an open cycle (2) & (4).

Why is the Krebs cycle called the TCA cycle?

When Krebs’ cycle process starts the acetyl CoA molecule reacts with oxaloacetate and produces citric acid or citrate. That is, the first compound produced in this cycle is citric acid. This citric acid is made up of tree carboxyl (COOH) groups. Hence the citric acid is called tricarboxylic acid and this cycle is known as TCA (tricarboxylic acid cycle) cycle (4).

Stages of Krebs cycle

The Krebs cycle is an oxidative pathway where acetyl CoA compounds are oxidized and produce carbon dioxide and water. Acetyl CoA acts as a connecting link between glycolysis and the Krebs cycle. This cycle supplies energy and provides many intermediates required for the synthesis of amino acids, glucose, etc. The cycle is completed in a few steps (1).

1. Formation of citrate

The process begins with the condensation of acetyl CoA and oxaloacetate to form citrate. The enzyme citrate synthase participates in this process. Here the two carbon atom acetyl CoA reacts with 4 carbon atom oxaloacetate molecules to form 6 carbon atoms of citrate. Acetyl CoA gives its acetyl group oxaloacetate to produce citrate. CoA is released and reacts with pyruvate.

2. Dehydration

In the second step citrate or citric acid removes one molecule of water and converts it into cis-aconitate or cis-aconitic acid (6 carbon atoms). This process is through the aconitase enzyme.

3. Hydration I

In this stage, cis-aconitate (6 carbon atoms) reabsorbs water and is converted into isocitrate or isocitric acid. This reaction also controls the aconitase enzyme. The transformation of citrate to isocitrate is one of isomerization.

Both cis-aconitate and isocitrate produced in the second and third stages contain tricarboxylic acids and 6 molecular carbon like the citric acid of the first stage (3).

4. Dehydrogenation I

In the fourth stage, isocitrate or isocitric acid is converted to oxalosuccinic acid or oxalosuccinate. This process occurs in the presence of isocitrate dehydrogenase enzymes. During the reaction of this enzyme, two molecules of hydrogen atoms removed are accepted by NAD⁺ to form NADH + H⁺. At the end of this reaction, the six-carbon oxalosuccinate is produced.

5. Decarboxylation I

Oxalosuccinate is formed α-ketoglutarate or α-ketoglutaric acid. This process is catalyzed by carboxylase enzymes. In this step, the carboxylase enzyme removes one molecule of CO₂ from oxalosuccinate (6 carbon atoms) and produces α-ketoglutarate or α-ketoglutaric acid (5 carbon atoms).

6. Dehydrogenation II

At this stage, α-ketoglutarate is produced in the presence of CoA and in the action of an enzyme called dehydrogenase to form succinyl CoA. During this reaction, one molecule of CO₂ is released as a by-product and one molecule of NAD⁺ is reduced by the removal of two molecules of hydrogen, and one molecule of NADH + H⁺ is produced.

7. Phosphorylation of ADP

Succinic acid or succinate is released from succinyl CoA by the action of the enzyme thiokinase. The energy released in this reaction is used to combine one molecule of inorganic phosphate with GDP and GDP is converted into GTP.

CoA is released in this process but in some cases, ADP takes part in the reaction instead of GDP, and one molecule of ATP is formed. One molecule of water is also produced in the conversion of succinyl CoA to succinic acid.

8. Dehydrogenation III

Succinic acid or succinate is oxidized to form fumarate or fumaric acid. This process is completed by the succinyl dehydrogenase enzyme. At this stage, Succinic acid or succinate loses two molecules of hydrogen and 4 carbon atoms of fumaric acid are formed.

In the reaction, two molecules of hydrogen are absorbed by the Flavin prosthetic group enzyme FAD (Flavin Adenine Dinucleotide) to form FADH₂.

9. Hydration II

Fumaric acid reacts with one molecule of water to form malic acid. The process is completed by the fumarase enzymes.

10. Dehydrogenation IV

In the last stage, malic acid is oxidized by NAD⁺ and converted to oxaloacetate or oxaloacetic acid. The Malate dehydrogenase enzyme regulates this reaction. The reduction of NAD⁺ occurs by 2 molecules of hydrogen removed using the energy generated in the reaction and NADH+ H⁺ is generated.

Oxaloacetate or oxaloacetic acid recombines with acetyl CoA to form citric acid or citrate. Thus the Krebs cycle is completed in a circular way (2) & (4).

The function of Krebs cycle

The Krebs cycle is the basic process of aerobic respiration. This cycle is the main source of energy production in the cell. So its function is very important. So of the important function of the cycle include:

1. It is used to derive chemical energy from proteins, fats, and carbohydrates. ATP is the energy molecule that is produced in this process. That is, the cycle combines fat, carbohydrates, and protein metabolism.

2. The cycle is used to precede the synthesis of amino acids.

3. The reactions of the cycle produce NADH molecules, which are reducing agents that are used in various biochemical reactions.

4. The citric acid cycle or Krebs cycle reduces the flavonoid adenine dinucleotide (FADH). Flavonoid adenine dinucleotide (FADH) is another source of energy.

5. The cycle is the central metabolic pathway because it connects directly or indirectly almost all individual metabolic pathways.

6. It plays an important role in the process of synthesis and energy production in cells (1) & (2).

How important is the Krebs cycle?

It is a very significant cycle in the respiration process.

1. 24 molecules of ATP are gained in a complete Krebs cycle. ATP is very important. It is the source of energy.

2. This cycle is very important for the body. This cycle utilizes about two-third of the total oxygen absorbed by the body.

3. Two atoms of pyruvic acid are produced from one molecule of glucose in this process.

4. About 10 ions of H⁺ and 3 molecules of CO₂ are produced from pyruvic acid in the Krebs cycle process. When the Krebs cycle is fully complete 20 ions of hydrogen and 6 molecules of carbon dioxide are produced.

5. This process is complete in the mitochondria. This process synthesis of ATP is complete by electrons. Each electron forms an ATP molecule in the Krebs cycle.

6. The hydrogen ions which are produced in the Krebs cycle enter and participate in the electron transport system (1) & (3).

Q&A

1. What are the products of the Krebs cycle?

NADH, carbon dioxide, ATP or GTP, and FADH2.

2. What is Krebs cycle?

The process by which pyruvic acid is completely oxidized under the influence of oxygen in the mitochondria and produces water, carbon dioxide and energy is called the Krebs cycle. ADP is converted into ATP in this cycle.

3. Where does Krebs cycle occur?

It occurs in all eukaryotic and prokaryotic cells in the matrix of mitochondria. And in prokaryotic cells, it is completed in the cytosol of the cell.

4. What does the Krebs cycle produce?

This produced 3 molecules of NADH, 2 molecules of carbon dioxide, one molecule of ATP or GTP, and one molecule of FADH2.

5. Where does Krebs cycle take place?

It takes place in all eukaryotic and prokaryotic cells. It takes place in the cytoplasm of a prokaryotic cell and in the mitochondria of a eukaryotic cell.

References

1. B Agarwal and V. K. Agarwal. Unified Botany, B.Sc. second Year. Shiva Lal Agarwal & Company Publications, Indore. Chapter: Respiration. Page no- 155 to 157.

2. B. Powar and G. R. Chatwal. Biochemistry, B. SC (general & honours course) and M. Sc. Himalaya publishing house, Chapter: Metabolism of carbohydrates. Page no- 410 to 413.

3. Ajoy Paul. Zoology Honours, volume- 2, Books & Allied (P) Ltd. Chapter: Carbohydrates metabolism. Page no- 294 to 302.

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