1 SURVEY OF BIOCHEMISTRY Electron Transport and Oxidative Phosphorylation

2 Redox Centers

3 The Mitochondrion Zoom in on the cristae: ~2000 per cell

4 How does electron transfer work? NADH binds to Complex I on the matrix side of the membrane

5 Electron Transfer with NADH NADH transfers its e - to redox centers in Complex I 2e - go to FMN… FMN resembles FAD without the adenine dinucleotide group

6 Electron Transfer with FMNH 2 NADH transfers 2e - to FMN - a redox center in Complex I FMNH 2 can then pass each e - to series of Fe-S clusters in a stepwise manner:

7 Fe-S Clusters in Complex I Complex I contains Fe-S clusters as cofactors

8 Coenzyme Q (Ubiquinone) Electrons pass from Fe-S clusters to a “mobile” electron carrier cofactor called Coenzyme Q

9 Electron Transfer with CoQ Coenzyme Q initially binds to Complex I to pick up 2 e - from the Fe-S clusters in Complex I

10 Complex II Succinate-Coenzyme Q Oxidoreductase FADH 2 Complex II is not shown Electrons pass from FADH 2 to CoQ via Complex II 4H + ions get pumped out of the matrix by Complex I and CoQ but not Complex II

11 Electron Transfer with CoQ Coenzyme Q binds to Complex III on the Intermembrane space side One e - goes to Cytochrome c One e - goes into the Q cycle

12 Electron Transfer with Cyt c Once CoQ loses its 2e -, it can dissociate from the upper region of Complex III and rebind near the matrix side and pick up the e - it just donated! Meanwhile, Cytochrome c carries its e - to Complex IV

13 Electron Transfer with Cyt c Another CoQ carrying 2e - can bind to Complex III, passing one of its e - to Cytochrome c and one into the Q cycle and ultimately to the original CoQ molecule.

14 Proton Pumping from Matrix NADHFMNFe-SCoQ 4 H + ions get pumped from matrix into the intermembrane space as 2 electrons are passed through Complex I (mechanism unknown)

15 Complex III and Complex IV Cytochrome bc 1 O H + 2H 2 O Cytochrome c oxidase How does ATP get made?

16 Chemiosmotic Theory Idea that the free energy needed to transport e - is conserved by the formation of a transmembrane proton gradient. Proton gradient drives ATP synthesis.

17 Complex V: ATP Synthase F 1 F 0 ATPase F 0 - water insoluble w/ 8 types of subunits F 1 - water soluble peripheral membrane protein w/ 5 types of subunits

18 Binding Mechanism in ATP Synthase O = openL = looseT = tight 1.ATP binds into the T protomer first 2.ADP and P i bind to the L protomer 3.Supply of energy induces a conformational change 4.ATP goes to the O protomer and is released 5.ATP is synthesized at the T protomer

19 Overview of Electron Transport Notice these inhibitors of electron transport!

20 Coordinated Control of Glycolysis and the TCA Cycle

21 Pros and Cons of Aerobic Metabolism Anaerobic Metabolism of Glucose: C 6 H 12 O ADP + 2 P i 2 Lactate + 2 H H 2 O + 2 ATP Aerobic Metabolism of Glucose: C 6 H 12 O ADP + 32 P i + 6O 2 6 CO H 2 O + 32 ATP PRO: Aerobic metabolism is up to 16x more productive than anerobic metabolism!

22 Pros and Cons of Aerobic Metabolism O 2 + e - O 2 - CON: Aerobic metabolism, with its high efficiency, tends to produce free radicals of oxygen! Superoxide radical Other harmful possibilities: H 2 O 2 + Fe 2+ OH + OH - + Fe 3+ O H 2 O 2 O 2 + H 2 O + OH

23 Superoxide Dismutase (SOD) An inherent antioxidant enzyme 2O H + O 2 + H 2 O 2 Catalase SOD 2H 2 O 2 2 H 2 O + O 2 Other potential antioxidants