Electron transport chain and inhibitor of etc

Electron transport chain and inhibitor

1. ELECTRON TRANSPORT CHAIN AND INHIBITOR OF ETC M.Sc Nutraceutical (Sem1) G.N.Khalsa College

2. Electron transport chain The electrons derived from NADH and FADH 2 combine with O 2 , and the energy released from these oxidation/reduction reactions is used to derived the synthesis of ATP from ADP. This transfer of electrons is done by multiple carriers which constitute the ELECTRON TRASPORT CHAIN (ETC). 2

3. Site of ETC - Mitochondria Fig 1 : Mitochondria 3

4. Overview Of Cellular Respiration ~38 ATP Fig 2 : Overview Of Cellular Respiration 4

5. Carriers in ETC Hydrogen carrier : Flavoprotien Ubiquinone or Co-enzyme Q Electron carrier : Iron sulphur protein Cytochrome HYDROGEN CARRIERS 1) FLAVOPROTEIN Protein tightly bound to FAM & FAD are called f alvoprotein. It is capable of accepting or donating one or two e - . 5

6. 2) Ubiquinone or Co-enzyme Q Is a lipid-soluble benzoquinon with a long isoprenoid side chain. Accept one electron to become the semiquinone radical (QH) or two electrons to form ubiquinol (QH2). It plays a central role in coupling electron flow to proton movement. Fig 3 : Ubiquinone 6

7. ELECTRON CARRIER Iron sulphur proteins : Containing Fe atom co-ordinate to sulphur of either Cys residue of protein or also with inorganic sulphur atoms. The Fe atoms are oxidised or reduced. There are 8 different Fe-S protein that function in mitochondrial e - transfer. Fig 4 : Fe-S protein 7

8. 2) Cytochromes : A proteins with a Fe-containing heme prostatic group, absorb light in visible range. Major respiratory Cytochromes- b, c or a. In ETC- Two a type cyt i.e. cyt a and a3. Two b type cyt i.e. cyt b1 and b2. Two c type cyt i.e. cyt c and c1. Cytochrome c is a key regulator of programme cell death in mammalian cells. 8 Fig 5 : Cytochrome b,c,a

9. Complexes in mitochondrial ETC Complex-I : NADH dehydrogenase . Complex-II : Succinate dehydrogenase . Complex-III : Cytochrome bc1 complex Complex IV : Cytochrome oxidise ATP synthesis 9 Fig 6 : Complexes of ETC

10. The Protein Components of the Mitochondrial- ETC Complex Name No. of Proteins Prosthetic Groups Complex I NADH Dehydrogenase 46 FMN, 9 Fe-S centres. Complex II Succinate- CoQ Reductase 5 FAD, cyt b 560 , 3 Fe-S centres. Complex III Co-Q- cyt c Reductase 11 cyt b, cyt c, Fe-S Complex IV Cytochrome Oxidase 13 cyt a, cyt a 3 , Cu-A, Cu-B 10 Table no.1

11. Is a large enzyme composed of 42 different polypeptide chains, including an FMN-containing flavoprotein and at least six iron sulphur clusters. It converts NADH to ubiquinone Over all reaction : 11 Reaction no.1 Complex-I : NADH DEHYROGENASE Fig 7: Complex I

12. It Converts Succinate to Ubiquinone and have 4 different protein. FAD is the initial e- acceptor Subunit B has three sets of Fe-S centres. Ubiquinone is bound to subunit C. A cardiolipin molecule is tightly bound to subunit C. Electrons move from succinate to FAD, then through the three Fe-S centres to ubiquinone. 12 succinate e- Complex II : Succinate dehydrogenase Fig 8: Complex 2

13. Complex III : Cytochrome bc1 complex Complex III converts ubiquinone to cytochrome c. Dimer of identical monomers, each with 11 different subunits. Within complex 3,the e- transferred to an Fe-S center and then to two b-type cytochromes or cytochrome c1. This transfer of protons involves the proton motive Q cycle. 13 Fig 9 : Complex 111 Reaction no.2

14. Complex IV: Cytochrome oxidase Converts cytochrome c to O 2 . It catalyses the transfer of electrons from reduced cyt c to molecular oxygen reducing it to H 2 O . 2 protons per pair of e - are pumped across the membrane and another two protons are transferred to molecular oxygen to form water. e- transfer : cyt c → CuA → cyt a → heme a3/CuB → O2 14 Fig 10 : Complex IV Reaction no.3

15. It consist of two multisubunit components F0 and F1 which are linked by a slender stalk. F0 provides channel for protons. F1 Phosphorylates ADP to ATP. 15 Fig 11 : ATP Synthase

16. SUMMARY 16 Fig 12 : Summary of ETC

17. INHIBITORS OF ETC 17 Fig 13 : Inhibitor oh ETC

18. BLOCKING ETC 18 Fig14 : Blocking site of ETC

19. 19 Inhibitor of electron transport chain COMPLEX Compound Target/mode of action I Piericidin Amobarbitol Rotenone Prevent electron transfer from Fe-S center to ubiquinone III Dimercaprol Antimycin A Blocks electron transfer from cytochrome b to cytochrome c1 IV Cyanide CO H2S Inhibit cytochrome oxidase Table no.2

20. Inhibitor of first site or complex-I 20

21. Inhibitor of Second site or complex-IV 21 Inhibitor of Second site or complex-III

22. THANK YOU 22