ATP _ Universal Carrier of Free Energy

Provides Energy for: _ Mechanical _ Chemical Work _ Ionic ATP _ Universal Carrier of Free Energy

Role of ATP in Metabolism Memorize this structure!!!! It’s the most important molecule in biochemistry.

TheConcept Energy rich molecules donate electrons to specific coenzymes to form energy-rich reduced coenzymes These electrons are donated to the electron transport chain to form ATP 1 pair of electrons is donated per each reduced coenzyme H2 = H + H H = 1 electron+ 1 proton :H¯ = 2 electrons+ 1 proton (Hydride ion) + H+ = 1 proton

Oxidized Reduced Electrochemical gradient

Carriers and transport systems are used to move ions and molecules across this membrane • Membrane convoluted or folded = ↑ Surface Area ATP Synthetase complex 50% protein Glycolysis Cytoplasm (Cristae) ElectronTransport Contains the ATP Synthetase complex • Inner mitochondrial membrane • Is the final common pathway • by which electrons from food • molecules are used to make • ATP and molecular oxygen • acts as the final acceptor • of the electrons

Citric acid cycle 2 e¯ 2 e¯ Citric acid cycle • Cytochromes ▬ Heme group ▬ Iron ▬ Ferric (Fe3+) ▬ Ferrous (Fe2+) Final acceptor of e-s is molecular oxygen NADH Dehydrogenase Cytochrome oxidase (Iron + copper) Complex V contains ATP Sythase • Series of Oxidation/Reduction reactions Electron transport chain ▬3 components • Flavoprotein ▬ NADH Dehydrogenase • CoQ (Quinone) ▬ Ubiquinone

Cyanide Each one of these inhibitors will completely stop electron transport and thus all ATP production

Three Main Tenets of the Mitchell Theory

FAD+ Blocked by atractyoside (Plant toxin) FADH2 ATP ADP ATP Synthase This dissipates gradient Oligomycin blocks Lower pH More protons pH gradient Electrical gradient ATP Cytoplasm 1 NADH = 3 ATP 1 FADH2 = 2 ATP ChemiosmoticHypothesis of Electron Transport coupled to ADP Phosphorylation ▬“Mitchell Hypothesis” Features: • Protons transported from the matrix to the inner mitochondrial space results • in an electric gradient and a pH gradient • As the protons flow through the membrane channel back into the matrix • they drive ATP synthesis Occurs with energy utilized by ATP synthase This proton transport couples electron transport to oxidative phosphorylation

O2 Electron Transport Electron transport coupled to phosphorylation of ADP  ATP ADP ADP ADP H2O ATP ATP ATP + Dinitrophenol (DNP) breaks down proton gradient Introduced in 1932 as weight reduction drug = Fatal hyperthermia High doses of aspirin ▬ results in fever O2 Electron transport continues Electron Transport No ADP phosphorylation Energy dissipated as heat H2O HEAT UncouplingofOxidativePhosphorylation

Breaks down proton gradient Brown adipose tissue creates heat by thermogenesis Thermogenin = uncoupling protein ▬ UCP1 Mechanism is to ↑ FA oxidation which uncouples oxidation phosphorylation The energy is given off as heat

Some mitochondrial myopathies caused by mutations in mtDNA InheritedDiseasesofOxidativePhosphorylation LIBER’S HEREDITARY OPTIC NEUROPATHY Bilateral loss of central vision occurs because of Neuroretinal degeneration Mutation in mitochondrial DNA Mitochondrial DNA is maternally inherited because allmitochondria come from the mother None come from the sperm because none from sperm enter the egg during fertilization 13 of the ~100 proteins in the mitochondrion are coded for by mtDNA Has mutation rate > 10x that of nuclear DNA

Glycerophosphate shuttle 2ATP for each NADH transported into mitochondrion from the cytoplasm Malate-Aspartate shuttle 3ATP for each NADH

1 2 3 6 4 7 5 8 2 Shuttle systems to bring cytosolic NADH into mitochondria for oxidative phosphorylation 1) Glycerophosphate shuttle = 36 ATP 2) Malate-aspartate shuttle = 38 ATP Count ATPs: Anerobic glycolysis = 2 Glycolysis + CAC + oxidative phosphorylation = 38

2 Domains F1 F0 . . . 1 ATP = 3.3 H+ Revolves at 100 Hz (revolutions/s) This is sufficient to produce a turnover of The weight of our body of ATP each day! ATPsynthase: • Rotates in 120° stages • 100 Hz one complete revolution = 3 ATP • Need 10 H+

Predicts the direction in which the Rx proceeds spontaneously Measures the change in the heat content of the reactants and products Bioenergetics _ Describes the transfer and utilization of energy in biologic systems Predicts if a reaction is possible Sign of DG predicts direction of the reaction NegativeDG √ Reaction goes spontaneously √ Is a net loss of energy = The Rx is Exergonic PositiveDG √ Reaction not spontaneous √ Energy must be added = The Rx is Endergonic ZeroDG and disorder. = Reactants are in equilibrium

ATP _ Universal Carrier of Free Energy