Cellular Respiration: Krebs Cycle and Oxidative Phosphorylation

Posted on Jan 12, 2025 in Biology

Krebs Cycle

Adolf Krebs discovered a series of oxidation-reduction reactions known as the Krebs Cycle. The cycle occurs in the mitochondrial matrix in eukaryotic cells, comprising a set of reactions that oxidize acetyl-coenzyme A to CO₂. The molecules NAD⁺ and FAD collect the electrons and are reduced to NADH and FADH₂. These electrons will be transferred to an electron transport chain, regenerating NAD⁺ and FAD to continue the Krebs Cycle.

Stages of the Krebs Cycle

1. Acetyl-coenzyme A binds to oxaloacetate to form citrate.
2. An isomerization reaction converts citrate into isocitrate.
3. Isocitrate is oxidized to oxalosuccinate, and NAD⁺ is reduced to NADH.
4. Oxalosuccinate is decarboxylated to form α-ketoglutarate and CO₂.
5. α-Ketoglutarate is converted to succinyl-coenzyme A. A molecule of NADH and a molecule of CO₂ are produced.
6. An H₂O molecule breaks the bond, releasing coenzyme A and yielding succinate.
7. An oxidation reaction converts succinate to fumarate.
8. Hydration of the double bond of fumarate leads to the formation of an alcohol group in malate.
9. Dehydrogenation of malate to oxaloacetate leads to the reduction of NAD⁺ to NADH.

Roles of the Krebs Cycle

1. Oxidation of acetyl-CoA to obtain 2 CO₂.
2. Production of reducing power in the form of NADH and FADH₂.
3. Generation of energy in the form of GTP.
4. Production of metabolic precursors for the synthesis of organic substances.

Overall Balance of the Krebs Cycle

Acetyl-CoA + 3 NAD⁺ + FAD + GDP + Pi + 2 H₂O → 2 CO₂ + 3 NADH + 3 H⁺ + FADH₂ + GTP + CoA

Respiratory Chain

The respiratory chain is located in the inner mitochondrial membrane and is formed by a group of enzymes and coenzymes. These molecules are oxidized and reduced, accepting and donating electrons from reduced coenzymes produced in the Krebs Cycle and the reactions of entry into the mitochondria.

The NADH formed in the cytoplasm during glycolysis cannot cross the inner mitochondrial membrane. To transfer electrons to the respiratory chain, it uses shuttle systems. There are two main systems: the glycerol-3-phosphate (G3P) shuttle, which assigns electrons to FAD, and the malate-oxaloacetate shuttle, which transfers electrons to NAD⁺.

Complexes of the Respiratory Chain

The members of the electron transport chain are grouped into five complexes that are part of the inner mitochondrial membrane. They are as follows:

• Complex I: NADH dehydrogenase transfers electrons to FMN and then to coenzyme Q.
• Complex II: Receives electrons from compounds such as succinate and also transmits them to CoQ.
• Complex III: Cytochrome b-c₁ accepts electrons from quinone (area between Complex I and III) and transfers them to the next complex.
• Cytochrome c is located between Complex III and IV.
• Complex IV: Cytochrome oxidase transfers electrons to O₂ to produce H₂O.
• Complex V: ATP synthase acts as a channel for the passage of protons from the intermembrane space to the mitochondrial matrix. It is here where energy is generated, resulting in the synthesis of ATP molecules.

Oxidative Phosphorylation

Oxidative phosphorylation is the primary source of energy for the cell. It is the process of ATP synthesis linked to electron transport in the mitochondrial respiratory chain. The energy released in these redox reactions is used to direct the synthesis of ATP from ADP. The electron transfer from NADH to O₂ is a reaction that releases a large amount of energy for each pair of electrons transferred.

The coupling mechanism of electron transport to ATP generation is explained by the chemiosmotic theory. The mitochondrial matrix is electronegative, while the intermembrane space is electropositive. The matrix pH is 8, while the intermembrane space is 7. This creates an electrochemical gradient of protons that can only cross the membrane through a channel in specific proteins. This allows the energy of the electrochemical gradient to be harnessed and converted into ATP through the action of the ATP synthase complex.

For each pair of electrons transferred from NADH, 3 ATP molecules are synthesized, whereas for each pair of electrons from FADH₂, 2 ATP molecules are synthesized.