Metabolic Pathways: Glycolysis and Krebs Cycle

Glycolysis, PDH Complex, Krebs Cycle, and ETS Pathways

• These pathways are crucial for energy production in cells.
• Glycolysis is the initial breakdown of glucose, occurring in the cytosol.
• The overall pathway of glycolysis is: Glucose + 2 NAD+ + 2 ADP + 2 P₁ → 2 Pyruvate + 2 NADH + 2 H+ + 2 ATP + 2 H₂O
• Glycolysis converts glucose to pyruvate, and also converts pyruvate to lactate in the absence of oxygen.
• Glycolysis involves 10 enzyme steps. Three of these are irreversible.
• In the presence of oxygen, pyruvate enters mitochondria, converting to acetyl-CoA.
• Acetyl-CoA enters the Krebs cycle for further breakdown.
• Lactate dehydrogenase (LDH) converts pyruvate to lactate in anaerobic conditions.
• Cancer cells sometimes use aerobic glycolysis, producing lactate even with oxygen present.
• Phosphorylation of glucose (to glucose-6-phosphate) prevents it from leaving cells.
• Hexokinase is a crucial regulatory enzyme in glycolysis, converting glucose to glucose-6-phosphate.
• The first step is converting glucose to glucose-6-phosphate by hexokinase, using one ATP.
  • This phosphorylation step is irreversible, trapping glucose within the cell.
• Glucose-6-phosphate is converted to fructose-6-phosphate.
  • This is isomerization and is catalyzed by phosphoglucose isomerase.
• Additional ATP used in glycolysis by phosphofructokinase to convert fructose-6-phosphate to fructose-1,6-bisphosphate.
  • This is a crucial regulatory step.
• A net of 2 ATP is produced per glucose molecule during glycolysis (a net gain of ATP).
• Glycolysis produces 2 NADH molecules.

Pyruvate Dehydrogenase Complex (PDH)

• Inside mitochondria, pyruvate is converted into acetyl-CoA by the PDH complex.
• This reaction involves an oxidative decarboxylation of pyruvate.
• The net reaction is: pyruvate + NAD+ + CoA → Acetyl-CoA + NADH + H+ + CO₂
• This step is irreversible. The PDH comprised of 3 enzymes:
  • E1: Pyruvate dehydrogenase
  • E2: An acetyltransferase
  • E3: Another dehydrogenase.
• The three enzyme complex is crucial for efficient transfer of intermediates.

Krebs Cycle (Citric Acid Cycle)

• The Krebs cycle is a central metabolic pathway in aerobic respiration, using acetyl-CoA to produce further energy.
• It was named after Hans Adolf Krebs who discovered it in 1937.
• Krebs cycle also known as the citric acid cycle and the tricarboxylic acid cycle (TCA).
• The Krebs cycle comprises 8 enzyme-catalyzed steps.
• Key molecules involved include citrate, isocitrate, and oxaloacetate.
• The cycle involves oxidation of carbon atoms in acetyl-CoA for energy production in the form of high energy molecules.
• NADH and FADH₂ are produced during the cycle, carrying high-energy electrons for further energy production.
• GTP, which can be converted to ATP, is also produced.

Electron Transport Chain (ETC) and Oxidative Phosphorylation

• ETC involves a series of protein complexes embedded in the inner mitochondrial membrane.
• High-energy electrons are carried from NADH and FADH₂ to the ETC.
• As electrons move through the ETC, protons are pumped across the inner mitochondrial membrane.
• This creates a proton gradient used by ATP synthase to produce ATP, a process called oxidative phosphorylation.
• The electron transport chain components work to maximize energy yields through the production of a proton gradient.
• The ETC has 4 complex protein clusters.
• Four protein clusters (complexes I, II, III, and IV) pump protons to generate a proton gradient which is used to produce ATP.
• Important molecules, such as NADH, FADH₂, ubiquinone (Coenzyme Q), and cytochromes, are also crucial to the ETC.
• Protons are pumped across the inner mitochondrial membrane due to the passing of electrons through the four complexes.
• The protons flow across the membrane's inner membrane through ATP synthetase which drives the formation of ATP.

Test your knowledge of metabolic pathways including glycolysis, PDH complex, Krebs cycle, and electron transport system. Understand how these pathways contribute to energy production in cells, the role of key enzymes, and the significance of anaerobic and aerobic conditions.