Krebs Cycle (Citric Acid Cycle)

The Krebs cycle’s primary purpose is to act as the principal energy source for cells and, thus, an essential part of cellular respiration.

In eukaryotic cells, it occurs in the matrix of the mitochondrion as it happens in the conversion of pyruvate to acetyl CoA. In prokaryotes, it happens in the cytoplasm. Both processes occur in the presence of oxygen.

The Krebs cycle is a closed loop, where the final product is used to form the first step. It is an eight-step process, which is as follows:

Its Steps

Step 1 – Citrate Synthesis: Here, the acetyl CoA condenses with the 4-carbon compound oxaloacetate to form a 6-carbon compound, citrate, releasing coenzyme A with the help of the enzyme citrate synthase.

Step 2 – Isomerization of Citrate: Next, the citrate gets converted to its isomer, isocitrate. The enzyme aconitase catalyzes this reaction.

Step 3 – Oxidative Decarboxylation of Isocitrate: Then, isocitrate undergoes dehydrogenation and decarboxylation to form 5C 𝝰-ketoglutarate. A molecular form of CO₂ is released. Isocitrate dehydrogenase, the rate-limiting enzyme of the cycle, catalyzes the reaction. It is an NAD⁺-dependent enzyme. Here, NAD⁺ is converted to NADH.

Step 4 – Oxidative Decarboxylation of Alpha-ketoglutarate: The 𝝰-ketoglutarate undergoes oxidative decarboxylation to form succinyl CoA, a 4C compound. The 𝝰-ketoglutarate dehydrogenase enzyme complex catalyzes the reaction. One molecule of CO₂ is released, and NAD⁺ is converted to NADH.

Step 5 – Cleavage of Succinyl Coenzyme A: In the next step, the succinyl CoA forms succinate. The enzyme succinyl CoA synthetase catalyzes the reaction. This step is coupled with substrate-level phosphorylation of GDP to get GTP. GTP transfers its phosphate to ADP, forming ATP.

Step 6 – Oxidation of Succinate: The succinate thus formed is oxidized by the enzyme succinate dehydrogenase to fumarate. In the process, FAD is converted to FADH₂.

Step 7 – Hydration of Fumarate: In this step, the fumarate gets converted to malate by adding one H₂O. The enzyme catalyzing this reaction is fumarase.

Step 8 – Oxidation of Malate: Malate is dehydrogenated to form oxaloacetate, which combines with another molecule of acetyl CoA and starts the new cycle. Hydrogens which are removed get transferred to NAD⁺, forming NADH. Malate dehydrogenase catalyzes the reaction.

Equation

2 Acetyl CoA + 6NAD⁺+ 2FAD + 2ADP + 2Pi → 4CO₂ + 6NADH + 6H⁺ + 2FADH₂ + 2ATP

Reactant:

• Acetyl CoA

Intermediates:

• Citrate
• Isocitrate
• Oxoglutarate
• Succinyl-CoA
• Succinate
• Fumarate
• Malate
• Oxaloacetate (the end product)

What are the Products of the Cycle: 

Thus one turn of the cycle produces:

• CO₂
• 3 NADH
• FADH₂
• GTP

An easy way to memorize the names of the compounds taking part in the Krebs cycle is through these sentences:

1. Citrate Is Krebs Starting Substrate For Making Oxaloacetate.

2. Our City Is Kept Safe and Sound From Malice.

C: Citrate

I: Isocitrate

K: Ketoglutarate

S: Succinyl-CoA

S: Succinate

F: Fumarate

M: Malate

O: Oxaloacetate

Krebs cycle, named from its discoverer Hans Kreb is an important part of aerobic cellular respiration in eukaryotes. It is also called the citric acid cycle from the first molecule, citrate it forms during the reaction or tricarboxylic acid (TCA) acid cycle due to the presence of three carboxyl groups on its first two intermediates.

The main purpose of the Krebs cycle is that it acts as the principal source of energy for cells and thus an important part of cellular respiration.

Prior to the krebs cycle, pyruvic acid (the product of glycolysis), which has three carbon atoms, is split apart and combined with coenzyme A, forming a two-carbon molecule acetyl-CoA. It then uses acetyl CoA and performs a series of redox reactions and stores the energy in reduced electron carriers NADH, FADH₂, and ATP. The electron carriers then pass their electrons into the electron transport chain and, through oxidative phosphorylation, generating most of the ATP in the cellular respiration.

In eukaryotic cells, it occurs in the matrix of the mitochondrion as it happens in the conversion of pyruvate to acetyl CoA. In prokaryotes it happens in the cytoplasm, both in the presence of oxygen.

The Krebs cycle is a closed loop, where the last product is used to form the first step. It is an eight-step process, which are as follows:

Its Steps

Step 1 – Citrate Synthesis: Here, the acetyl CoA condenses with the 4-carbon compound oxaloacetate to form a 6-carbon compound, citrate, releasing coenzyme A with the help of the enzyme citrate synthase.

Step 2 – Isomerization of Citrate: Next, the citrate gets converted to its isomer, isocitrate. The enzyme aconitase catalyzes this reaction.

Step 3 – Oxidative Decarboxylation of Isocitrate: Then, isocitrate undergoes dehydrogenation and decarboxylation to form 5C 𝝰-ketoglutarate. A molecular form of CO₂ is released. Isocitrate dehydrogenase, the rate limiting enzymeof the cycle catalyzes the reaction. It is an NAD⁺-dependent enzyme. Here, NAD⁺ is converted to NADH.

Step 4 – Oxidative Decarboxylation of Alpha-ketoglutarate: The 𝝰-ketoglutarate undergoes oxidative decarboxylation to form succinyl CoA, a 4C compound. The reaction is catalyzed by the 𝝰-ketoglutarate dehydrogenase enzyme complex. One molecule of CO₂ is released, and NAD⁺ is converted to NADH.

Step 5 – Cleavage of Succinyl Coenzyme A:  In the next step, the succinyl CoA forms succinate. The enzyme succinyl CoA synthetase catalyzes the reaction. This is coupled with substrate-level phosphorylation of GDP to get GTP. GTP transfers its phosphate to ADP, forming ATP.

Step 6 – Oxidation of Succinate: The succinate thus formed is oxidized by the enzyme succinate dehydrogenase to fumarate. In the process, FAD is converted to FADH₂.

Step 7 – Hydration of Fumarate: In this step, the fumarate gets converted to malate by adding one H₂O. The enzyme catalyzing this reaction is fumarase.

Step 8 – Oxidation of Malate: Malate is dehydrogenated to form oxaloacetate, which combines with another molecule of acetyl CoA and starts the new cycle. Hydrogens which are removed, get transferred to NAD+ forming NADH. Malate dehydrogenase catalyzes the reaction.

Equation

2 Acetyl CoA + 6NAD++ 2FAD + 2ADP + 2Pi → 4CO₂ + 6NADH + 6H⁺ + 2FADH₂ + 2ATP

Reactant

• Acetyly CoA

Intermediates

• Citrate
• Isocitrate
• Oxoglutarate
• Succinyl-CoA
• Succinate
• Fumarate
• Malate
• Oxaloacetate (the end product)

What are the Products of the Krebs Cycle

Thus one turn of the cycle produces:

•  CO₂
• 3 NADH
• FADH₂
• GTP

A quick way to memorize the names of the compounds taking part in the Krebs cycle is through these sentences:

1. Citrate Is Krebs Starting Substrate For Making Oxaloacetate.

2. Our City Is Kept Safe and Sound From Malice.

C: Citrate

I: Isocitrate

K: Ketoglutarate

S: Succinyl-CoA

S: Succinate

F: Fumarate

M: Malate

O: Oxaloacetate