Bioenergetics and Oxidative Phosphorylation 2024 PDF

Bioenergetics and Oxidative Phosphorylation Lynn O’Connor 2024 ETC https://www.youtube.com/watch?v=LQmTKxI4Wn4 https://www.youtube.com/watch?v=rdF3mnyS1p0 ATP synthase https://www.youtube.com/watch?v=WzqVu8OWedo&feature=youtu.be...

Bioenergetics and Oxidative Phosphorylation Lynn O’Connor 2024 ETC https://www.youtube.com/watch?v=LQmTKxI4Wn4 https://www.youtube.com/watch?v=rdF3mnyS1p0 ATP synthase https://www.youtube.com/watch?v=WzqVu8OWedo&feature=youtu.be 1  Inner life of the cell https://www.youtube.com/watch?v=B_zD3Nx SsD8 2  Bioenergetics Transfer and utilization of energy in biological systems Changes in free energy G allow you to predict whether a reaction takes place - Looks only at initial and final states 3 G – change in free energy Go - standard free energy change Negative G – net loss of energy –rxn goes spontaneously as measured (exergonic) Positive G - net gain of energy – requires energy input to proceed (endergonic) G is zero - reactants are in equilibrium The free energy of the forward and backwards rxns are equal in magnitude but opposite in sign 4  ΔG and the conc of reactants and products ΔG of the reaction A to B depends on the concentration of reactant and product At constant temp and pressure the following relationship can be derived ΔG = ΔGo + RT ln [B]/[A] A reaction with a +ive ΔGo can proceed in the forward direction if the ratio of products to reactants ([B]/[A])is sufficiently small or ratio of reactants to products is large 5 Coupling chemical reactions 6 7  ATP as an Energy Carrier Couple endergonic to exergonic reactions e.g ATP hydrolysis ATP = Adenosine (adenine + ribose) to which 3 phosphate groups are attached Remove 1 phosphate -ADP Remove 2 phosphates - AMP Standard free energy of hydrolysis of ATP Go = -7.3 kcal/mol for each of the two terminal phosphates  ATP is called a high-energy phosphate compound 8 Electron Transport Chain 9  ETC https://www.youtube.com/watch?v=xbJ0nbzt5Kw Location: Inner mitochondrial membrane Advantages: highly convoluted Contains 5 separate protein complexes called Complex I,II,III,IV,V Complexes 1-IV each contain part of the ETC Complexes accept or donate electrons to the relatively mobile electron carriers, coenzyme Q and cytochrome c Electrons ultimately combine with O2 and protons to form water REQUIREMENT FOR O2 make the ETC the respiratory chain The respiratory chain accounts for the greatest portion of the body’s use of O2 – this is why we breath 10  Reactions of the ETC The flow of electrons is shown by the arrows 11  Site-specific inhibitors Inhibition of electron transport inhibits ATP synthesis 12  Phosphorylation of ADP to ATP The transfer of electrons through ETC is energetically favourable NADH is a strong electron donor O2 is a strong electron acceptor 13  Chemiosmotic Hypothesis 1. Proton Pump: Electron transport is coupled to the phosphorylation of ADP by the pumping of protons across the inner mit membrane Pumped from matrix to the intermembrane space Occurs at Complexes I,III and IV The process creates an electrical gradient (more +ive charges on the outside of the membrane than on the inside Also creates a pH gradient (outside of the membrane is at a lower pH than the inside) The energy generated by the proton is sufficient to drive ATP synthesis 14 Electron transport shown in association with the transport of proton 15  ATP synthase https://www.youtube.com/watch?v=CN2XOe_c0iM A multisubunit enzyme Synthesizes ATP using the energy of the proton gradient It works Protons pumped to the cytosolic side of the inner mit membrane re-enter the matrix by passing through a proton channel in Fo domain This drives rotation of the c ring of Fo Simultaneously this dissipates the pH and electrical gradients Fo rotation causes conformation changes in the  subunit of the F1 that allows them to bind ADP and Pi, phosphorylate ADP to ATP and release ATP 16  https://www.youtube.com/watch?v=lO1oXQ3eS_s https://www.youtube.com/watch?v=lOgea89L1UY https://www.youtube.com/watch?v=3y1dO4nNaKY https://www.youtube.com/watch?v=b_cp8MsnZFA ETC https://www.youtube.com/watch?v=rdF3mnyS1p0 ATP synthase: https://www.youtube.com/watch?v=XI8m6o0gXDY The inner life of the cell full version: https://www.youtube.com/watch?v=-Au5_2LMd5k 17 Coupling in oxidative phosphorylation ATP synthesis is coupled to ETC through the proton gradient –reflects the metabolic needs and uses Oligomycin (an antibiotic that inhibits ATPase) Binds to the Fo – closes the proton channel and prevents re-entry of protons into the matrix This prevents phosphorylation of ADP to ATP ETC stops Respiratory control: The dependency of cellular respiration on the ability to phosphorylate ADP to ATP 18 Uncoupling proteins (UCPs) Occur in the inner mit membrane of mammals Form channels that allow protons to reenter the mit matrix without energy being captured as ATP Energy is released as heat – nonshivering thermogenesis UCP1 (thermogenin) – heat production in the brown adipose tissue of mammals Brown fat cells – 90% of respiratory energy is used for thermogenesis – prevalent in neonates and hibernating animals 19 Synthetic uncouplers 1. Classic example is 2,4-dinitrophenol Lipid soluble. Proton carrier Readily diffuses through mit membrane ETC is accelerated- ATP not produced – heat is produced 2. Aspirin and other salicylates also lipid soluble and has a dissociable proton In high conc salicylate to partially uncouple mitochondria The decline in ATP conc and consequent increase in AMP in the cytosol stimulates glycolysis Overstimulation of glycolysis results in increased lactic acid- metabolic acidosis 20