ATP motors

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  • 1. Mechanochemistry

2. Mechanochemistryisthecouplingofthemechanicalandthe chemicalphenomenaonamolecularscale. Molecular motorsarebiologicalmolecularmachinesthatare theessentialagentsofmovementinlivingorganisms. Amotormaybedefinedasadevicethatconsumesenergyin oneformandconvertsitintomotionormechanicalwork;for example,manyprotein-basedmolecularmotorsharnessthe chemicalfree energyreleased by thehydrolysisofATPin ordertoperformmechanicalwork 3. Examples Cytoskeletalmotors Myosinisresponsibleformusclecontraction Dyneinproducesbeatingofciliaandflagella Polymerisationmotors MicrotubulepolymerizationusingGTP. Rotarymotors: FoF1-ATP synthasefamilyofproteinsconvertthechemicalenergyinATPtothe electrochemicalpotentialenergyofaprotongradientacrossamembraneor theotherwayaround. The bacterial flagellumresponsible for the swimming and tumbling of bacteriaactsasarigidpropellerthatispoweredbyarotarymotor. Nucleicacidmotors: RNA polymerasetranscribesRNAfromaDNAtemplate 4. TheMotorofLife Anenzymewithinourbody'scellscalledanATP Synthase. Likeanyothermotoritrotates,andsurprisinglyfast-infact atabout6,000revsperminute! Further, it is the last word in ultra-miniaturisation, being 200,000timessmallerthanapinhead! Wehavesome100trillion(1followedby14zeros)cells,there are in excess of 10 quadrillion (1 followed by 16 zeros) of theseamazingultra-tinylittlemotorswhichdriveourbodies anduponwhichourverylivesdepend! The ATP Synthase motor's job is to manufacture a little molecule called ATP - short for Adenosine triphosphate - which is of enormous importance for the successful functioningofourbodies. 5. The food we eat is ultimately converted into energy 6. Oxidativephosphorylation Process in which ATP is formed as a result of transfer of electronsfromNADHorFADH2toO2byaseriesofelectron carriers. Alloxidativestepsinthedegradationofcarbohydrates,fats, and amino acids converge at this final stage of cellular respiration, in which the energy of oxidation drives the synthesisofATP. Thisprocesstakesplaceinmitochondrion Majorsourceofenergyinourbody. 36-38 molecules of ATP are produced when glucose is completelyoxidizedtoCO2andH2O. 7. Mitochondrion: SiteforATPsynthesis 8. TheRespiratorychain Anelectron transport chain (ETC)coupleselectrontransferbetween anelectron donor(such asNADH) and an electron acceptor(such asO2) withthetransferofH+ ions(protons)acrossamembrane.The resultingelectrochemical proton gradientis used to generatechemical energyin the form ofadenosine triphosphate. If protons flow back through the membrane, they enable mechanical work, such as rotating bacterialflagella.ATP synthase, an enzyme converts this mechanical energy into chemical energy by producing ATP,which powers most cellularreactions. 9. ETC The electron transport chain comprises an enzymatic series of electron donors and acceptors. Each electron donor passes electrons to a more electronegative acceptor, which in turn donates these electrons to another acceptor, a process that continues down the series until electrons are passed to oxygen, the most electronegative and terminal electron acceptor in the chain. Passage of electrons between donor and acceptor releases energy, which is used to generate a proton gradient across the mitochondrial membrane by actively pumping protons into the intermembrane space. This electrochemical proton gradient allows ATP synthase to use the flow of H+ through the enzyme back into the matrix to generate ATP from ADP and inorganic phosphate. 10. Oxidative phosphorylation begins with the entry of electrons into the respiratory chain via electron carriers- nicotinamide nucleotides (NAD or NADP) or flavin nucleotides (FMN or FAD). NAD+ + 2H+ + 2e- NADH + H+ NADP+ + 2H+ + 2e- NADPH + H+ FMN or FAD can accept 1 e- + 1 H+ to become semiquinone form or 2 e- + 2 H+ to form FMNH2 or FADH2 . 11. Respiratory chain consists of four complexes Complex I (NADH coenzyme Q reductase): accepts electrons from the Krebs cycle electron carrier nicotinamide adenine dinucleotide (NADH), and passes them to coenzyme UQ (ubiquinone) Complex II (succinate dehydrogenase): also passes electrons to UQ. Complex III (cytochrome bc1 complex): passes electrons to cyt c Complex IV (cytochrome c oxidase) recieves electrons from cyt c and uses the electrons and hydrogen ions to reduce molecular oxygen to water. 12. ETC 13. Complex I Two electrons are removed from NADH and transferred to ubiquinone (Q). The reduced product, ubiquinol (QH2) freely diffuses within the membrane, and Complex I translocates four protons (H+ ) across the membrane, thus producing a proton gradient. 14. Complex II Additional electrons are delivered into the quinone pool (Q) originating from succinate and transferred (via FAD) to Q. 15. Complex III Two electrons are removed from QH2 and sequentially transferred to two molecules of cytochrome c 16. Complex IV four electrons are removed from four molecules of cytochrome c and transferred to molecular oxygen (O2), producing two molecules of water. At the same time, four protons are translocated across the membrane, contributing to the proton gradient. 17. Proton gradient powers synthesis of ATP Flow of electrons from NADH to oxygen is an exergonic process which is coupled to ATP synthesis, an endergonic process. 18. Chemiosmotic Theory Peter Mitchell proposed that electron transport and ATP synthesis are coupled by a proton gradient across the inner mitochondrial membrane. The transfer of electrons through the respiratory chain leads to the pumping of protons from the matrix to the cytosolic side of the inner mitochondrial membrane. The H+ concentration becomes lower in the matrix, and an electrical field with the matrix side negative is generated. Mitchell's idea, called the chemiosmotic hypothesis, was that this proton-motive force drives the synthesis of ATP by ATP synthase 19. ATP motors ATP synthase (mitochon-drial ATPase or F1-F0 ATPase or Complex V) is an important enzyme that provides energy for the cell to use through the synthesis of adenosine triphosphate (ATP). ATP is the most commonly used "energy currency" of cells from most organisms. It is formed from adenosine diphosphate (ADP) and inorganic phosphate (Pi), and needs energy. ATP synthase + ADP + Pi ATP Synthase + ATP 20. ATP synthase Is located within the mitochondria ATP synthase consists of 2 regions the FO portion is within the membrane. The F1 portion of the ATP synthase is above the membrane, inside the matrix of the mitochondria. 21. Fo-F1 complex It is a large, complex membrane-embedded enzyme that looks like a ball on a stick. The 85- diameter ball, called the F1 subunit, protrudes into the mitochondrial matrix and contains the catalytic activity of the synthase. The F1 subunit consists of five types of polypeptide chains (33). The and subunits, which make up the bulk of the F1, are arranged alternately in a hexameric ring. Both bind nucleotides but only the subunits participate directly in catalysis. The central stalk consists of two proteins: and . The subunit includes a long a-helical coiled coil that extends into the center of the 33hexamer. Each of the subunits interacts with a different face of . 22. The F0 subunit is a hydrophobic segment that spans the inner mitochondrial membrane. F0 contains the proton channel of the complex. This channel consists of a ring comprising from 10 to 14 c subunits that are embedded in the membrane. A single a subunit binds to the outside of this ring. The proton channel depends on both the a subunit and the c ring. The F0 and F1 subunits are connected in two ways, by the central stalk and by an exterior column. The exterior column consists of one a subunit, two b subunits, and the subunit. 23. ATP Synthase as Motor Protein: The Binding Change Mechanism ATP synthesis is coupled with a conformational change in the ATP synthase generated by rotation of the gamma subunit. the proton-motive force across the inner mitochondrial membrane, generated by the electron transport chain, drives the passage of protons through the membrane via the FO region of ATP synthase. The changes in the properties of the three subunits allow sequential ADP and Pi binding, ATP synthesis, and ATP release. 24. interactions with the gamma subunit make the three b subunits inequivalent. The three subunits can exist in three different conformations: T, or tight, conformation: binds ATP with great avidity to convert bound ADP and Pi into ATP L, or loose, conformation: binds ADP and Pi but is sufficiently constrained that it cannot release bound nucleotides. O, or open, form: exist with a bound nucleotide but it can also convert to form a more open conformation and release a bound nucleotide. 25. The interconversion of these three forms can be driven by rotation of the subunit. If the subunit is rotated 120 degrees in a counterclockwise direction there will be a change in the subunit in the T conformation into the O conformation, allowing the subunit to release the ATP that has been formed within it. The subunit in the L conformation will be converted into the T conformation, allowing the transition of bound ADP + Pi into ATP. Finally, the subunit in the O conformation will be converted into the L conformation, trapping the bound ADP and Pi so that they cannot escape. 26. Rotational catalysis: The subunit rotates in 120-degree increments, with each step corresponding to the hydrolysis of a single ATP molecule. 27. Proton Motion Across the Membrane Drives Rotation of the C Ring The c subunit consists of two a helices with an aspartate at 61 position. The a subunit contains two proton half channels. A proton enters from the intermembrane space into the cytosolic half- channel to neutralize the charge on an aspartate residue in a c subunit. With this charge neutralized, the c ring can rota