Electron Transport Chain

Electron transport chain • • • •

Electrons pass through cytochrome C Some energy of the reaction is used to transport protein across the membrane Oxidation of NADH is a transport of 10 protons creating a gradient Complex 1 NADH Dehydrogenase o ultiple subunits o High hydrophilic globular domain o !arge hydrophobic domain bound by inner mitochondrial membrane o 1 step  NADH is oxidi"ed to NAD# $hich releases % electrons &N is reduced to &NH% Contains multiple '() iron sulfide clusters All in the globular part of the en"yme • *here is no ubi+uinome prosthetic bound to the en"yme ,- is reduced to ,-H% by using the % electrons .. *here is a thermodynamic dri/ing force for the reduction of NADH *he ron Sulfer clusters ha/e a reduction potential t is a proton pump ' are pumped across the membrane by the component that is o  bound to the inner mitochondrial membrane) Complex % ,- is reduced to ,-H% o o  subunits o Electrons released by the oxidation of &ADH%2 pass through the iron sulfer clusters % electrons are used to reduce ,- to ,-H% o Contains 1 molecule of heme 'staying in either the %# or 3# state)2 this position o ma4es it thought that it could be on the electron transport path$ay2 but that5s not the case Does not pump protons o Complex 3 Oxidi"es ,-H% to ,o *o go from ,- to the anion is a reaction that in/ol/es 1 electron to no protons o then to go from the intermediate to ,-H% re+uires 1 electron and % protons o Carries electrons to complex  - cycle *he 67phase of the membrane becomes enriched in positi/e charges o o En"yme 3 oxidi"es ,-H% to ,One site is to$ards the 6 side '-6 site) *he other is opposite ,-H% is oxidi"ed o % protons are released *he electron is used to reduce an iron sulfer cluster   

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,-H% turns to ,o ,- turns to ,-7 Second half  o *$o ,-H% turns to ,,- turns to ,-H% Complex  6roduces the oxidi"ed form of Cytochrome C o Oxygen is the final place that electrons go 'terminal electron acceptor) o *o reduce one atom of oxygen to $ater % e lectron must go do$n the path$ay o *he en"yme is a proton pump o 8eleasing energy to dri/e conformational changes % protons are pumped per % electrons that mo/e through the en"yme o E*C 9enerally thought that the protons of : succinate and 10 NADH o %%0 is the amount of energy released by the release of one mole of NADH o Amount of energy released by NADH oxidation is the same as the amount of o energy needed to pump protons out 

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A*6 Synthase Embedded in the intermitochondrial membrane 'the globular component in o located in the matrix) *here is a hydrophobic component is embedded in the membrane '& o) *he subunit A is membrane bound and > 'this 4eeps the top bound • do$n) goes out of the membrane and up to the matrix ultiple C subunits ma4e up the ring '< in this picture2 can go as • high as 1= in other species) *here is an aspartic residue on one of the rings in the o subunit 'this residue is negati/ely charged) this lines up $ith a arginine residue in the A subunit forming a fa/orable charge to charge interaction ?hen this gets protonated due to the flo$ of  protons2 the entire C subunit ma4es a rotation2 re+uires a number of protons e+ual to the number of  C subunits Spins in a countercloc4$ise direction $hich is dri/en by a flo$ of •  protons through proton channels *he globular component is comprised of 3 alpha and 3 beta 'acti/e sites $here o AD6 is phosphorylated to A*6) components $ith a gamma unit in the center *he globular section does not rotate o *he rotation of the globular section rotates 3 times and gi/es 3 A*6 o 

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At physiologic conditions AD6 is more positi/ely charged th an A*6 by one unit *he proton gradient dri/es this process Exporting A*6 from this system costs 1 proton form the gradient Ho$ many A*6 is made $hene/er % electrons pass through the system@ &or each NADH that is oxidi"ed there are 10 protons pumped out *herefore to ma4e 1 molecule of A*6 it ta4es 3 1;3 protons are re+uired ithe5s Hypothesis is that the membrane must permeable for protons *he model ho$e/er sho$s other$ise Effecti/e uncouple Bit collapse the proton gradient an d introduces a direct  path$ay across the membrane if this happens that no $or4 is done and energy is dissipated as heat Oxygen consumption $ill continue *his might also increase the flo$ of protons *hese uncouplers can be used as a source of heat DN6 is a good uncoupler 

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