Cellular Respiration: Krebs Cycle, Electron Transport Chain
Krebs Cycle
The Krebs cycle is the oxidation of the acetyl group of acetyl-CoA to CO2, while reducing NAD and FAD. These reduced coenzymes are subsequently reoxidized by the respiratory chain, generating ATP. It consists of a series of eight enzymatically catalyzed reactions that occur in the mitochondrial matrix:
- Acetyl-CoA condenses with oxaloacetate to yield citrate, a tricarboxylic acid.
- Citrate is converted to isocitrate.
- Oxidative decarboxylation of isocitrate yields alpha-ketoglutarate, forming CO2 and NADH + H+.
- Alpha-ketoglutarate is oxidatively decarboxylated, yielding succinyl-CoA, CO2, and NADH + H+. At this point, the acetyl group has been completely oxidized.
- Succinyl-CoA is converted to succinate, with the formation of GTP via substrate-level phosphorylation. The following reactions regenerate oxaloacetate.
- Succinate is oxidized to fumarate, with FAD being reduced to FADH2.
- Fumarate is hydrated to form malate.
- Oxidation of malate to oxaloacetate produces NADH + H+.
Respiratory Chain
The respiratory chain’s goal is the oxidation of reduced coenzymes. It consists of a chain of molecules that are reduced and oxidized as electrons and protons are passed between them. This electron transport chain is located in the inner mitochondrial membrane (cristae). The components include:
- NADH dehydrogenase complex
- Coenzyme Q reductase complex
- Cytochromes a-a3 complex
Finally, cytochrome a3 transfers electrons to molecular oxygen, which is the final electron acceptor. At each redox step, the released energy is used for ATP synthesis, a process called oxidative phosphorylation.
The accepted model to explain this process is Mitchell’s chemiosmotic hypothesis: the released energy is used to pump protons from the mitochondrial matrix to the intermembrane space. This generates an electrochemical gradient. When H+ ions flow back into the matrix through F particles, they provide the energy for ATP synthesis.
Oxidation of Fatty Acids
- Activation: The fatty acid is activated by binding to CoA, forming acyl-CoA. This reaction occurs in the cytoplasm and requires ATP.
- Acetyl-CoA enters the mitochondria with the help of carnitine. It then undergoes successive cycles of four enzymatic reactions: oxidation, hydration, oxidation, and thiolysis. This results in the successive release of two-carbon fragments from the carboxyl end of acyl-CoA. At the end of each cycle, one molecule of acetyl-CoA and a new acyl-CoA (with two fewer carbon atoms) are formed.
The acetyl-CoA molecules formed in successive cycles of beta-oxidation enter the catabolic pathway of the Krebs cycle.
Protein Catabolism
Although proteins are not the primary metabolic fuels, their constituent units can be oxidized for energy. Their degradation comprises:
- Deamination: Removal of the amino group. This occurs in the cytoplasm and mitochondria of hepatocytes. Because NH3 is a highly toxic substance (it increases pH to dangerous levels), plants and animals have developed protective systems:
- Plants: Store substances as alkaloids.
- Animals: Eliminate it by transformation into urea (mammals) or uric acid (birds).
Anabolism
Anabolism is the constructive pathway of metabolism, the synthesis route. If the starting molecules are inorganic, it is called autotrophic anabolism; if they are organic, it is called heterotrophic anabolism. This process is very similar in all organisms. In autotrophs, if light energy is used, it is called photosynthesis, and if the energy released in certain oxidation reactions is used, it is called chemosynthesis.
Photosynthesis
It is the conversion of light energy into chemical energy (ATP), which is then used for the synthesis of organic matter. This is possible because photosynthetic pigments can capture light energy.