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• TCA cycle
• Glycolysis
• Beta oxidation
1. TCA Cycle (Tricarboxylic Acid Cycle / Krebs Cycle)
The TCA cycle is a central metabolic pathway that takes place in the mitochondrial matrix. It plays a key role in the oxidation of Acetyl-CoA—derived from carbohydrates, fats, or proteins—to produce energy. The cycle not only generates high-energy molecules that drive ATP production in the Electron Transport Chain but also provides intermediates for various biosynthetic processes.
Key Steps:
• Condensation: Acetyl-CoA (2 carbons) combines with Oxaloacetate (4 carbons) to form Citrate (6 carbons).
• Isomerization: Citrate is rearranged into Isocitrate.
• First Oxidative Decarboxylation: Isocitrate is oxidized to α-Ketoglutarate (5 carbons), producing NADH and releasing CO₂.
• Second Oxidative Decarboxylation: α-Ketoglutarate is further oxidized to Succinyl-CoA (4 carbons), generating another NADH and releasing CO₂.
• Substrate-Level Phosphorylation: Succinyl-CoA is converted into Succinate, yielding ATP (or GTP).
• FADH₂ Production: Succinate is oxidized to Fumarate, resulting in the production of FADH₂.
• Hydration: Fumarate is converted to Malate.
• Final Oxidation: Malate is oxidized to regenerate Oxaloacetate, producing a final NADH.
Products per Cycle:
• NADH: 3 molecules (fuel the Electron Transport Chain)
• FADH₂: 1 molecule
• ATP (or GTP): 1 molecule
• CO₂: 2 molecules
2. Glycolysis
Glycolysis is the initial stage of cellular respiration, taking place in the cytoplasm. It breaks down one molecule of glucose (a six-carbon sugar) into two molecules of pyruvate, generating energy and reducing power.
Phases and Steps:
• Energy Investment Phase:
• Phosphorylation: Glucose is phosphorylated to form Glucose-6-Phosphate.
• Isomerization and Second Phosphorylation: Glucose-6-Phosphate is rearranged to Fructose-6-Phosphate, which is then phosphorylated to Fructose-1,6-bisphosphate using ATP.
• Cleavage Phase:
• Splitting the Molecule: Fructose-1,6-bisphosphate is split into two three-carbon sugars, dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). DHAP is converted into G3P so that two molecules of G3P continue through the pathway.
• Energy Payoff Phase:
• Conversion to Pyruvate: Each G3P molecule is oxidized and converted into pyruvate, producing a total of 4 ATP (with a net gain of 2 ATP after subtracting the 2 ATP used) and 2 NADH.
Net Products (per glucose molecule):
• 2 Pyruvate molecules
• 2 NADH molecules
• 2 ATP molecules (net gain)
3. Beta-Oxidation
Beta-oxidation is a catabolic process where fatty acids are broken down to generate acetyl-CoA, which then enters the Krebs cycle for energy production, and occurs in the mitochondria.Â
Key Steps:
• Activation: A fatty acid is activated in the cytoplasm by conjugation with Coenzyme A (CoA) to form fatty acyl-CoA.
• Transport: The fatty acyl-CoA is transported into the mitochondria via the carnitine shuttle.
• Repeated Cycles: Once inside the mitochondria, the fatty acyl-CoA undergoes cycles of reactions:
• Oxidation: The acyl-CoA is oxidized, forming a double bond and producing FADH₂.
• Hydration: Water is added across the double bond, forming β-hydroxyacyl-CoA.
• Second Oxidation: β-hydroxyacyl-CoA is oxidized to β-ketoacyl-CoA, producing NADH.
• Thiolysis: β-ketoacyl-CoA is cleaved by Coenzyme A, releasing a two-carbon Acetyl-CoA unit and leaving behind a shortened acyl-CoA that re-enters the cycle.
Products per Cycle:
• Acetyl-CoA: Enters the TCA cycle for further oxidation.
• NADH and FADH₂: Serve as electron carriers to drive ATP production in the Electron Transport Chain.
Overall Importance:
Beta-oxidation provides a highly efficient means of extracting energy from fats, especially during periods of fasting or extended exercise, as fats yield more ATP per molecule compared to carbohydrates.