1. CYTOCHROME C OXIDOREDUCTASE

2. INTRO…  Also known as Cytochrome Reductase, Q- Cytochrome C oxidoreductase or Complex III of ETC.  This complex is an integral part of the mitochondrial respiratory chain.  contributing to the generation of electrochemical potential ( Δμ +) by catalyzing the electron transfer (ET) reaction from ubiquinol (QH )to cytochrome c coupled to proton translocation across the membrane.  Helps in ATP generation.

4. STRUCTURE  Transmembrane protein located in inner mitochondrial membrane.  Monomer consist of 3-11 subunits (polypeptide chains)  Q-cytochrome C oxidoreductase contains three hemes: two b-type hemes within cytochrome b, and one c- type heme within cytochrome c 1.  Enzyme also contains an iron-sulfur protein with an 2Fe-2S center.

5. REACTIONS :  It catalyzes the reduction of cytochrome c by oxidation of coenzyme Q (CoQ) and the concomitant pumping of 4 protons from the mitochondrial matrix to the intermembrane space:  QH 2 + 2 cytochrome c (Fe III ) + 2 H + in → Q + 2 cytochrome c (Fe II ) + 4 H + out  In the process called Q cycle, two protons are consumed from the matrix, four protons are released into the inter membrane space and two electrons are passed to cytochrome c.

6. Q-CYCLE The reaction mechanism for complex III (cytochrome bc1, coenzyme Q: cytochrome C oxidoreductase) is known as the ubiquinone ("Q") cycle. THE REACTION MECHANISM FOR COMPLEX III (CYTOCHROME BC1, COENZYME Q: CYTOCHROME C OXIDOREDUCTASE) IS KNOWN AS THE UBIQUINONE ("Q") CYCLE. OVERALL :  2 X QH 2 OXIDISED TO Q  1 X Q REDUCED TO QH 2  2 X CYT C REDUCED  4 X H+ RELEASED INTO INTERMEMBRANE SPACE  2 X H + PICKED UP FROM MATRIX Overall  2 x QH 2 oxidised to Q.  1 x Q reduced to QH 2  2 x Cyt c reduced.  4 x H+ released into intermembrane space.  2 x H + picked up from matrix

7. INHIBITORS: There are three distinct groups of Complex III inhibitors:-  Antimycin A: binds to the Q i site and inhibits the transfer of electrons in Complex III from heme b H to oxidized Q (Qi site inhibitor).  Myxothiazol and stigmatellin : binds to the Q o site and inhibits the transfer of electrons from reduced QH 2 to the Rieske Iron sulfur protein  Myxothiazol binds nearer to cytochrome bL (hence termed a "proximal" inhibitor).  Stigmatellin binds farther from heme bL and nearer the Rieske Iron sulfur protein, with which it strongly interacts.

8. DEFICENCIES: A genetic condition that can affect several parts of the body. It is also known as Isolated CoQ- cytochrome c reductase deficiency or Ubiquinone-cytochrome c oxidoreductase deficiency, it causes:  Myopathy & Muscle fatigue  Tubulopathy  Encephalopathy  Psychomotor delay  Cardiomyopathy  Lactic acidosis  Hyperglycemia Mitochondrial complex III deficiency can be fatal in childhood, although individuals with mild signs and symptoms can survive into adolescence or adulthood.

9. MUTATIONS:  Mutations in BCS1L, and MT-CYB gene is responsible for proper maturation of complex III, can result in BJORNSTAD syndrome and the GRACILE syndrome, which in neonates are lethal conditions that have multisystem and neurologic manifestations typifying severe mitochondrial disorders.

10. References:  https://proteopedia.org/wiki/index.php/Complex_III_of_Electron_Transport _Chain https://proteopedia.org/wiki/index.php/Complex_III_of_Electron_Transport _Chain  http://www.aklectures.com/lecture/q-cycle-and-complex-iii-of-electron- transport-chain http://www.aklectures.com/lecture/q-cycle-and-complex-iii-of-electron- transport-chain  https://www.life.illinois.edu/crofts/bioph354/bc-complex_summary.html https://www.life.illinois.edu/crofts/bioph354/bc-complex_summary.html  https://www.genenames.org/data/genegroup/#!/group/642 https://www.genenames.org/data/genegroup/#!/group/642  https://www.youtube.com/watch?v=CKBeQYr66TQ https://www.youtube.com/watch?v=CKBeQYr66TQ

11. THANKYOU