Krebs Cycle

Introduction

The Krebs cycle steps are a cycle of enzymatic reactions in all aerobic organisms and are a central driver of cellular respiration. It is also known as the citric acid cycle. The first intermediate formed in this cycle in aerobic respiration is citric acid. The Krebs cycle takes place in the mitochondrial matrix, the dense solution inside the mitochondria. It is one of the most critical reaction sequences in biochemistry. The Krebs cycle is part of the larger glucose metabolism, whereby glucose is oxidized to form pyruvate. This series of reactions releases stored energy through acetyl-CoA oxidation derived from carbohydrates, fats, and proteins. Krebs cycle is after the name Hans Krebs, who first elucidated the cycle. He got his Nobel prize in 1953 for his contribution.

Krebs cycle 

The first-ever Krebs cycle was observed in the muscle tissue of a pigeon. It takes place in all types of cells, either eukaryotic or prokaryotic cells. The Krebs cycle in eukaryotic organisms occurs in the matrix of the mitochondria. The Krebs cycle in the prokaryotic organisms occurs in the cytosol of the cell.

The process of glycolysis forms the pyruvate within the cytoplasm. Other reactions occur in the mitochondria. Thus, pyruvate is transported there. There are different enzymes present both in the inner membrane and matrix of mitochondria.

Krebs Cycle Steps

The steps of the Krebs cycle are as follows:

Step 1- The first step of the Krebs cycle involves condensation. The acetyl CoA condenses with oxaloacetate (4C) to form citrate (6C), and coenzyme A releases. The enzyme Citrate synthase is responsible for catalyzing the reaction. 

Step 2: Step two of the Krebs cycle involves the conversion of citrate to isocitrate, its isomer. The aconitase enzyme catalyzes the second step of the Krebs cycle, i.e., this reaction. 

Step 3: Step 3 of the Krebs cycle involves the dehydrogenation and also the decarboxylation of isocitrate forming 𝝰-ketoglutarate (5C). CO2 molecules release in this reaction. The catalyst of this reaction is isocitrate dehydrogenase. Step 3 of the Krebs cycle converts NAD+ into NADH.

Step 4: The oxidative decarboxylation of α-ketoglutarate (5C) produces succinyl CoA (4C). α-ketoglutarate dehydrogenase enzyme catalyzes the reaction. NAD+ converts to NADH.

Step 5: In step 5 of Krebs cycles, the Succinyl CoA converts to succinate. Succinyl CoA synthetase carries out this reaction. This enzyme couples with substrate-level phosphorylation of GDP and causes the formation of GTP. This GTP is responsible for transferring its phosphate to ADP. It results in the formation of ATP.

Step 6: In step 6 of the Krebs cycle, the succinate (produced in step 5) oxidizes to fumarate. It occurs by the action of the enzyme succinate dehydrogenase. In step 6, the FAD converts to FADH2.

Step 7: Now, in step 7, the Fumarate conversion occurs. It gets converted to malate by the addition of one water molecule. The enzyme fumarase catalyzes this reaction. 

Step 8: Step 8 or the last step of the Krebs cycle causes the dehydrogenation of Malate forming oxaloacetate. This oxaloacetate now combines with another molecule of acetyl CoA. And the cycle starts all over again. The enzyme, Malate dehydrogenase catalyzes the reaction of the last step of the Krebs cycle.

Equation of Krebs Cycle

Acetyl CoA + 3 NAD+ + 1 FAD + 1 ADP + 1 Pi → 2 CO2 + 3 NADH + 3 H+ + 1 FADH2 + 1 ATP 

In other words,

Acetyl CoA + Nicotinamide adenine dinucleotide + Flavin adenine dinucleotide + Adenosine diphosphate + Phosphate → Pyruvate + Water + Adenosine triphosphate + Nicotinamide adenine dinucleotide + Hydrogen ions

Products of Krebs cycle 

• CO2 released as waste
• NADH and FADH2 also move to the next stage (of cellular respiration)
• Energy released in the form of ATP. A glucose molecule produces two molecules of ATP because two pyruvate molecules are created from each glucose molecule
• At the end of the Krebs cycle, the final product is oxaloacetic acid. This resembles the oxaloacetic acid that eventually begins the cycle

Enzymes in Krebs cycle

The enzymes that catalyze the various steps throughout the process of the citric acid cycle (Krebs cycle) are as follows:

• Citrate synthase
• Aconitase
• Isocitrate dehydrogenase
• α-ketoglutarate
• Succinyl-CoA synthetase
• Succinate dehydrogenase
• Fumarase
• Malate dehydrogenase

Importance of Citric Acid Cycle (Krebs Cycle)

The importance of the citric acid cycle is in the following processes:

• Lipid Metabolism
• Amino Acid Metabolism
• Energy Expenditure
• Metabolomics
• Protein Metabolism (Turnover)
• Glucose Metabolism

Conclusion 

The Krebs cycle is an important process of the production of energy during aerobic respiration in different organisms. There are 8 basic Krebs cycle steps. The first step produces citrate as a by-product. Therefore, the Krebs cycle is also known as the Citric acid cycle. Different enzymes take place during the reaction, such as Citrate synthase, Aconitase, Isocitrate dehydrogenase, α-ketoglutarate, Succinyl-CoA synthetase, Succinate dehydrogenase, Fumarase and Malate dehydrogenase. The Products of the Krebs cycle in different steps are CO2, NADH and FADH2, ATP (the unit of energy). The end product of the citric acid or tricarboxylic acid cycle is oxaloacetate. The importance of the Citric acid cycle is in different metabolic processes, such as Lipid Metabolism, Amino Acid Metabolism, Energy Expenditure, Metabolomics, Protein Metabolism (Turnover) and Glucose Metabolism.