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 Multiple subunitso High hydrophilic globular domain o Large hydrophobic domain bound by inner mitochondrial membrane o 1 step

NADH is oxidized to NAD+ which releases 2 electrons FMN is reduced to FMNH2 Contains multiple (9) iron sulfide clusters

All in the globular part of the enzyme There is no ubiquinome prosthetic bound to the enzyme UQ is reduced to UQH2 by using the 2 electrons ^^ There is a thermodynamic driving force for the reduction of NADH The Iron Sulfer clusters have a reduction potential

o It is a proton pump (4 are pumped across the membrane by the component that is bound to the inner mitochondrial membrane)

Complex 2 o UQ is reduced to UQH2o 4 subunits o Electrons released by the oxidation of FADH2, pass through the iron sulfer

clusters o 2 electrons are used to reduce UQ to UQH2o Contains 1 molecule of heme (staying in either the 2+ or 3+ state), this position

makes it thought that it could be on the electron transport pathway, but that’s not the case

o Does not pump protons Complex 3

o Oxidizes UQH2 to UQo To go from UQ to the anion is a reaction that involves 1 electron to no protons

then to go from the intermediate to UQH2 requires 1 electron and 2 protons o Carries electrons to complex 4

Q cycleo The P-phase of the membrane becomes enriched in positive chargeso Enzyme 3 oxidizes UQH2 to UQ

One site is towards the P side (QP site) The other is opposite

o UQH2 is oxidized 2 protons are released

The electron is used to reduce an iron sulfer cluster UQH2 turns to UQ

o UQ turns to UQ-o Second half

Two UQH2 turns to UQ UQ turns to UQH2

Complex 4 o Produces the oxidized form of Cytochrome C o Oxygen is the final place that electrons go (terminal electron acceptor) o To reduce one atom of oxygen to water 2 electron must go down the pathway o The enzyme is a proton pump

Releasing energy to drive conformational changes o 2 protons are pumped per 2 electrons that move through the enzyme

ETCo Generally thought that the protons of 6 succinate and 10 NADH o 220 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

energy needed to pump protons out

12/8/15

ATP Synthase o Embedded in the intermitochondrial membrane (the globular component in

located in the matrix) There is a hydrophobic component is embedded in the membrane (F o)

The subunit A is membrane bound and B (this keeps the top bound down) goes out of the membrane and up to the matrix

Multiple C subunits make up the ring (8 in this picture, can go as high as 15 in other species)

o There is an aspartic residue on one of the rings in the subunit (this residue is negatively charged) this lines up with a arginine residue in the A subunit forming a favorable charge to charge interaction

When this gets protonated due to the flow of protons, the entire C subunit makes a rotation, requires a number of protons equal to the number of C subunits

Spins in a counterclockwise direction which is driven by a flow of protons through proton channels

o The globular component is comprised of 3 alpha and 3 beta (active sites where ADP is phosphorylated to ATP) components with a gamma unit in the center

o The globular section does not rotate o The rotation of the globular section rotates 3 times and gives 3 ATP o At physiologic conditions ADP is more positively charged than ATP by one unit o The proton gradient drives this process o Exporting ATP from this system costs 1 proton form the gradient o How many ATP is made whenever 2 electrons pass through the system?

For each NADH that is oxidized there are 10 protons pumped out o Therefore to make 1 molecule of ATP it takes 3 1/3 protons are required o Mithe’s Hypothesis is that the membrane must permeable for protons. The model

however shows otherwise o Effective uncouple “it collapse the proton gradient and introduces a direct

pathway across the membrane” if this happens that no work is done and energy is dissipated as heat. Oxygen consumption will continue. This might also increase the flow of protons. These uncouplers can be used as a source of heat. DNP is a good uncoupler