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Renin Angiotensin Mechanism.

Krebs Cycle.

 

Definition:

The Krebs cycle is a series of enzyme catalyzed reactions occurring in the mitochondria, where acetyl-CoA is oxidized to form carbon dioxide and coenzymes are reduced, which generate ATP in the electron transport chain.

  • Krebs cycle was discovered by Hans Krebs, and was awarded the Nobel prize in 1953.

  • Also called,

    • TCA Cycle (Tricarboxylic Acid Cycle)

    • Citric Acid Cycle.

  • It is an eight-step process. 

  • Krebs cycle or TCA cycle takes place in the matrix of mitochondria under aerobic condition.

Steps of Krebs Cycle:

  1. Step 1: 

    • The first step is the condensation of acetyl CoA (2C) with 4-carbon compound oxaloacetate to form 6C citrate.

    • coenzyme A is released. 

    • Enzyme: Citrate synthase.

  2. Step 2: 

    • Citrate is converted to its isomer, isocitrate. 

    • Enzyme: Aconitase.

  3. Step 3: 

    • Isocitrate undergoes dehydrogenation and decarboxylation to form 5C 𝝰-ketoglutarate. 

    • CO2 is released. 

    • Enzyme: Isocitrate dehydrogenase. 

    • NAD+ is converted to NADH. ( Gain of 3 ATPs)

  4. Step 4: 

    • 𝝰-ketoglutarate gets converted to succinyl CoA, a 4C compound. 

    • Enzyme: 𝝰-ketoglutarate dehydrogenase. 

    • One molecule of CO2 is released. 

    • NAD+ is converted to NADH. ( Gain of 3 ATPs)

  5. Step 5: 

    • Succinyl CoA gets converted to succinate. 

    • Enzyme: Succinyl CoA synthetase. 

    • Converts GDP to get GTP. 

    • GTP transfers its phosphate to ADP forming ATP.

  6. Step 6: 

    • Succinate is oxidized to fumarate. 

    • Enzyme: Succinate dehydrogenase.

    • FAD is converted to FADH2.

  7. Step 7: 

    • Fumarate gets converted to malate by the addition of one H2O. 

    • Enzyme: Fumarase.

  8. Step 8: 

    • Malate is dehydrogenated to form oxaloacetate, which combines with another molecule of acetyl CoA and starts the new cycle. 

    • Hydrogens removed, get transferred to NAD+ forming NADH. (Gain of 3 ATPs)

    • Enzyme: Malate dehydrogenase.

Energetics of Krebs Cycle:

  • Each Krebs cycle forms the following products:

  • 2 molecules of CO2 are released. Removal of CO2 or decarboxylation of citric acid takes place at two places:

    • In the conversion of isocitrate (6C) to 𝝰-ketoglutarate (5C)

    • In the conversion of 𝝰-ketoglutarate (5C) to succinyl CoA (4C)

  • 1 ATP is produced in the conversion of succinyl CoA to succinate

  • 3 NAD+ are reduced to NADH and 1 FAD+ is converted to FADH2 in the following reactions:

    • Isocitrate to 𝝰-ketoglutarate → NADH

    • 𝝰-ketoglutarate to succinyl CoA → NADH

    • Succinate to fumarate → FADH2

    • Malate to Oxaloacetate → NADH

  • Note that 2 molecules of Acetyl CoA are produced from oxidative decarboxylation of 2 pyruvates so two cycles are required per glucose molecule.

  • Krebs cycle yields 4 CO2, 6 NADH, 2 FADH2 and 2 ATPs.

  • Each molecule of NADH can form 3 ATPs and each FADH2 gives 2 ATPs on oxidation in the electron transport chain.

  • Krebs Cycle Yields 24 ATPs.

Significance of Krebs Cycle:

  • It is the final pathway of oxidation of glucose, fats and amino acids.

  • Amino acids (metabolic product of proteins) are deaminated and get converted to pyruvate and other intermediates of the Krebs cycle. They enter the cycle and get metabolized e.g. alanine is converted to pyruvate, glutamate to 𝝰-ketoglutarate, aspartate to oxaloacetate on deamination

  • Fatty acids undergo 𝞫-oxidation to form acetyl CoA, which enters the Krebs cycle

  • It is the major source of ATP production in the cells. 

  • It plays an important role in gluconeogenesis and lipogenesis and interconversion of amino acids.

  • Many intermediate compounds are used in the synthesis of amino acids, nucleotides, cytochromes and chlorophylls, etc.

  • Vitamins play an important role in the citric acid cycle. Riboflavin, niacin, thiamin and pantothenic acid as a part of various enzymes cofactors (FAD, NAD) and coenzyme A.

  • Regulation of Krebs cycle depends on the supply of NAD+ and utilization of ATP in physical and chemical work.

  • The genetic defects of the Krebs cycle enzymes are associated with neural damage.

Commonly Asked Questions.

  1. Write in detail about Krebs Cycle.

  2. Write significance of Krebs cycle.

  3. Describe Krebs Cycle stating its energetics.
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