Lecture Details[]
Janet Macaulay; Week 2 MED1011; Biochemistry
Lecture Content[]
Cells produce energy through the electron transport chain and chemiosmosis. The electron transport chain utilises NADH, H and FADH2 from glycolysis, pyruvate oxidation and the citric acid cycle and regenerates NAD, FAD and produces ATP and H2O. It transfers electrons to release energy. Most enzymes and other electron carriers in the chain are located in the inner mitochondrial membrane. Cytochromes contain iron and are a part of this. High energy electrons are transported to NADH-Q reductase which pumps hydrogen from the matrix to th intermembrane space. They then move to ubiquinones, cytochrome c reductase, cytochrome c (located outside the cell), cytochrome c oxidase and then to ATP synthase. As it moves it loses energy to pump out protons. II is located on the inner surface of the membrane. O2 is the final acceptor of protons and electrons, forming H2O.
- 1/2O2 + 2H + 2e -> H2O
Two protons are consumed which contribute to proton gradient across the inner mitochondrial membrane. As the electrons move down the ETC they lose energy, captured by protein pumps that actively transport H out of the mitochondrial matrix, establishing a gradient of proton concentration and electric charge (proton motive force). This proton gradient causes H ions to move through ATP synthase down the concentration gradient, producing energy to transform ADP binding to phosphate to form ATP. For each molecule of glucose used fermentation yields 2 ATP, glycolysis with pyruvate oxidation, CAC and ETC produces up to 32 (36 if optimal) molecules of ATP. If a tissue is deprived of oxygen ETC is inhibited, ATP decreases, anaerobic glycolysis is activated, lactic acid levels increase, intracellular pH decreases, hypoxic cells swell, enzymes leak through permeable membrane -> cell death, however hypoxia is reversible (important for organ transplantation).
Dysfunction in oxidative phosphorylation causes Leigh disease, severe lactic acidosis, neurological abnormalities. Inhalation of hydrogen cyanide or ingestion of potassium cyanide causes inhibition of ETC by decoupling of ATP synthesis, tissue asphyxia notably of CNS.