Krebs Cycle

Krebs Cycle or Citric Acid Cycle

The Krebs cycle, also known as the Citric Acid Cycle, consists of enzyme-driven reactions in the mitochondrial matrix where acetyl-CoA is oxidized to produce carbon dioxide and reduced coenzymes that generate ATP in the electron transport chain.

Named after Hans Krebs, who described the cycle in detail and won the Nobel Prize in 1953, it involves eight steps where acetyl-CoA is converted to carbon dioxide, producing ATP, NADH, and FADH2 in the process. Each glucose molecule results in two acetyl-CoA, so the cycle runs twice per glucose, producing four CO2, six NADH, two FADH2, and two ATP.

Krebs Cycle in Cellular Respiration

Cellular respiration, a four-stage catabolic process, breaks down nutrients to release energy stored as ATP, releasing waste products. In aerobic respiration, oxygen is essential. Each glucose molecule can produce 36-38 ATPs.

Four Stages of Cellular Respiration:

1. Glycolysis: Partial breakdown of glucose into two pyruvate molecules in the cytosol.
2. Formation of Acetyl CoA: Pyruvate enters the mitochondrial matrix and forms acetyl CoA.
3. Krebs Cycle: Complete oxidation of acetyl CoA occurs, producing ATP, NADH, and FADH2.
4. Electron Transport and Oxidative Phosphorylation: Electrons from NADH and FADH2 are transferred to oxygen, generating ATP in the inner mitochondrial membrane.

Krebs Cycle Steps

1. Formation of Citrate: Acetyl CoA combines with oxaloacetate to form citrate.
2. Formation of Isocitrate: Citrate rearranges to isocitrate.
3. Formation of α-Ketoglutarate: Isocitrate is oxidized to α-ketoglutarate, releasing CO2 and forming NADH.
4. Formation of Succinyl CoA: α-Ketoglutarate converts to succinyl CoA, releasing CO2 and forming NADH.
5. Formation of Succinate: Succinyl CoA converts to succinate, producing ATP.
6. Formation of Fumarate: Succinate is oxidized to fumarate, forming FADH2.
7. Formation of Malate: Fumarate converts to malate.
8. Regeneration of Oxaloacetate: Malate is oxidized to regenerate oxaloacetate, forming NADH.

Krebs Cycle Summary

• Location: Mitochondrial matrix
• Reactants: Acetyl CoA and oxaloacetate
• Products per cycle: 2 CO2, 1 ATP, 3 NADH, 1 FADH2

Since each glucose forms two acetyl CoA, the cycle runs twice per glucose, yielding:

• 4 CO2
• 2 ATP
• 6 NADH
• 2 FADH2

Krebs Cycle Equation

Significance of the Krebs Cycle

• Oxidation Pathway: Final stage for glucose, fats, and amino acids oxidation.
• Energy Source: Major source of ATP in cells.
• Metabolic Intermediates: Produces compounds for gluconeogenesis, lipogenesis, and amino acid synthesis.
• Role of Vitamins: Essential vitamins (riboflavin, niacin, thiamin, and pantothenic acid) function as enzyme cofactors.
• Regulation: Depends on NAD+ supply and ATP use.
• Genetic Defects: Linked to neural damage.
• Liver Function: Critical for many processes; liver damage affects the cycle significantly.

Summary

The Krebs cycle is essential for energy production in cells, producing ATP and intermediates necessary for various biochemical pathways. It operates efficiently in the mitochondrial matrix and integrates with other cellular respiration stages to fully oxidize glucose.

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