Metabolism and Bioenergetics Lecture Notes PDF

Lippincott’s illustrated reviews Chapter 6, Page 69 Lectures 10 Metabolism and Bioenergetics 1  Specific Objectives By the end of this lecture students can be able to: Understand the synthesis of ATP. Explain electr...

Lippincott’s illustrated reviews Chapter 6, Page 69 Lectures 10 Metabolism and Bioenergetics 1  Specific Objectives By the end of this lecture students can be able to: Understand the synthesis of ATP. Explain electron transport chain. Understand the action of uncouplers. 2  Cellular Energy Adenosine Triphosphate ATP 1. adenine: nitrogenous base 2. ribose: five carbon sugar 3. phosphate group: chain of 3 adenine phosphate group P P P ribose 3  Three phosphate groups-(two with high energy bonds Last phosphate group (PO4) contains the MOST energy It is estimated that each cell will generate and consume approximately 10,000,000 molecules of ATP per second 4  Coupled Reaction - ATP The exergonic hydrolysis of ATP is coupled with the endergonic dehydration process by transferring a H2O phosphate group to another molecule. H2O 5  Hydrolysis of ATP ATP + H2O ADP + P (exergonic) Adenosine triphosphate (ATP) P P P Hydrolysis (add water) P P + P Adenosine diphosphate (ADP) 6  Dehydration of ATP ADP + P ATP + H2O (endergonic) Dehydration (Remove H2O P P + P Adenosine diphosphate (ADP) Adenosine triphosphate (ATP) P P P 7  ELECTRON TRANSPORT CHAIN Most constituents of the respiratory chain are embedded in the inner mitochondrial membrane matrix inter- cristae membrane space inner outer membrane mitochondrion membrane 8  Energy-rich molecules, such as glucose, are metabolized by a series of oxidation reactions EE ultimately yielding CO2 and water. The metabolic intermediates of these reactions donate electrons to specific coenzymes— nicotinamide adenine dinucleotide (NAD+) Ideas and flavin adenine dinucleotide (FAD)—to form the energy-rich reduced coenzymes, NADH and FADH2.  Tuple Copyright Cmassengale 10  These reduced coenzymes (NADH 0 and FADH2) c can, in turn, each donate a pair of electrons to a specialized set of electron carriers, collectively called the electron transport chain. in inner mitochondrial membrane As electrons are passed down the electron transport chain, they lose much of their free energy.  Protons (H+) are pumped from the mitochondrial matrix to the intermembrane space forming concentration gradient of the hydrogen ions (Protons). This activates ATP synthase enzyme which capture the free energy and stored it by production of ATP from ADP and inorganic phosphate (Pi). Oxygen is finally reduced to form water. 12  About 40% energy is trapped. The remainder of the free energy not trapped as ATP is used to: Drive ancillary reactions such as Ca2+ transport into mitochondria, and Generate heat.  Energetics of ATP Synthesis When NADH is oxidized, about 3 ATP molecules are generated. When FADH2 is oxidized, about 2 ATP molecules are generated. 14  Oxidative Phosphorylation couple The transfer of electrons from the reduced coenzymes through the respiratory chain to oxygen is known as biological oxidation. Energy released during this process is trapped as ATP, this is called phosphorylation. This coupling of oxidation with phosphorylation is called oxidative phosphorylation. 15 Copyright Cmassengale 16  Uncouplers (UCPs) Electron transport and phosphorylation can be uncoupled by compounds that increase the permeability of the inner mitochondrial membrane to protons. The classic example is 2,4-dinitrophenol, a lipophilic proton carrier that readily diffuses through the mitochondrial membrane. 17  This uncouple causes electron transport to proceed at a rapid rate without establishing a proton gradient, much as do the UCPs. Again, energy is released as heat rather than being used to synthesize ATP. This explains the fever that accompanies toxic overdoses of these drugs. Another Examples for uncouplers: Physiological uncouplers: Bilirubin, long chain free fatty acids and Thyroxin, in high levels. 088 In high doses, aspirin and other salicylates uncouple oxidative phosphorylation. 18  0 Ionophores are lipid soluble compounds that increase the permeability of lipid bilayers to certain ions. There are two types of ionophores; mobile ion carries (e.g. valinomycin) and channel formers (e.g. gramicidin). Valinomycin allows potassium to permeate mitochondria and dissipate the proton gradient. 08 Calcium ions stimulate dephosphorylation process. 19  Inherited defects in oxidative phosphorylation Mutations in mitochondrial DNA (mtDNA) are responsible for several diseases, including some cases of mitochondrial myopathies and Leber hereditary optic neuropathy. Leber hereditary optic neuropathy (LHON) is a disease in which bilateral loss of central vision occurs as a result of neuroretinal degeneration, including damage to the optic nerve. 20  Primary LHON mutation caused decreased cellular respiration and lower mitochondrial complex I specific activity. Copyright Cmassengale 21 Copyright Cmassengale 22 Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 23