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Organization Of The Electron Transport Chain

Location: the enzymes of electron transport chain are located in inner mitochondrial membrane.
  1. Complex i is point of entry into etc electrons from NADH
    1. This enzyme complex is called NADH-coenzyme Q Reductase or NADH dehydrogenase
    2. Prosthetic groups – FMN, Fe-S
    3. The electron acceptor for complex I is coenzyme Q
    4. Inhibitors – Rotenone, Amobarbital, Piericidin A, Chlorpromazine
  2. Complex ii is the point of entry into the electron transport chain for electrons from succinate.
    1. This enzyme complex is called succinate-Q-reductase.
    2. Prosthetic groups – FAD, Fe-S
    3. Inhibitors – Carboxin, Malonate
    4. No energy (ATP produced at complex II)
  3. Coenzyme Q- highly lipid soluble molecule firmly embedded in membrane. In accepts electrons from both complex I and complex II and donates electrons to complex III.
  4.   Complex III Is Electron Acceptor For Coenzyme Q
    1. This enzyme complex is called cytochrome reductase.
    2. Prosthetic groups – Haem b – 562; Haem b- 566, Haem C1; Fe-S
    3. Electron acceptor for complex III is cytochrome c
    4. Inhibitors – BAL and antimycin A, Phenformin
  5. Cytochrome c: Cytochrome c mediates transfer of electron from complex III to complex IV Prosthetic group : Heme
  6.  Complex Iv Is The Electron Acceptor For Cytochrome C
    1. This enzyme complex is called cytochrome oxidase.
    2. Prosthetic group – copper, Heme (cytochrome a and cytochrome a3)
    3. The electron acceptor for complex IV is molecular oxygen.
    4. Inhibitors – carbon monoxide & H2S, cyanide and axide

Bioenergetics Of ETC


  1. The redox difference between NADH &  oxygen is +1.14 volts which is equivalent to energy 52.6kcal/mol
  2. Phosphorylation of ADP to ATP requires 7.3kcal/mol
  3. Oxidation of 1 NADH releases 52.6kcal/mol energy, enough to make several ATP. The 52.6kcal/mol is not released in one reaction but is released in small packets. The bulk of the energy which is enough to transport protons across the inner membrane is released by 3 reactions involving complexes I, III and IV.
  4. The Sites are Electrons pass from :
    1. NADH through the FMN to FeS proteins of complex I.
    2. cyt b to cyt c1 in complex III.
    3. cyt a to oxygen in complex IV.
  1. Oxidative Phosphorylation is the process is which ATP is formed as a result of transfer of electrons from NADH or FADH2 to O2 by a series of electron carriers.
    The flow of electrons from NADH or FADH2 to O2 through protein complexes located in inner mitochondrial membrane leads to pumping of protons out of mitochondrial matrix generating a proton motive force.

Recent Advances



  1. Chemiosmotic theory of oxidative phosphorylation
    1. An electrochemical gradient of protons H+ across the mitochondrial inner membrane, serves to couple energy flow of electron transport to the formation of ATP.
    2. In electron transport chain, as electron moves down the chain, H+ is transferred from mitochondrial matrix to the intermembrane space.
    3. The protons in the intermembrane space pass through inner membrane & back into matrix by ATP synthase.
    4. ATP synthase is coenzyme complex that synthesizes ATP.ATP synthase consists of two units.
      1. F0- spans the membrane and is composed of four subunits. It is the channel through protons cross the membrane
      2. F1 units is composed of five subunits & contains catalytic site for ATP synthesis.
  2. Efficiency Of Oxidative Phosphorylation
    Oxidation of 1 NADH releases 52.6kcal/mol of energy. From this, energy equivalent to 3ATP i.e. about 22 kcal/mol is trapped. Thus about 40% energy is trapped and the rest is dissipated as heat

Inhibitors Of Etc And Oxidative Phosphorylation

  1. Inhibitors Of Etc And Site

Inhibitors Of Oxidative Phosphorylation And Mechanism                           

  1. Oligomycin   – completely blocks oxidation and phosphorylation in intact mitochondria
                         – Inhibitors of ATP synthase
  2. Actractyloside  – inhibits oxidative phosphorylation that is dependent on transport of adenine nucleotides across the inner mitochondrial membrane.
    It inhibits transport of ADP into mitochondrion and of ATP out of mitochondria.
  3. Bongregate  – Same as Actractyloside. It is the toxin of pseudomonas.
Extra Edge

The redox carriers are grouped into four respiratory chain complexes in the inner mitochondrial membrane. Three of the four complexes are able to use the energy released in the redox gradient to pump protons to the outside of the membrane, creating an electrochemical potential between the matrix and the inner membrane space, while complex II does not pump protons and does not create redox gradient.


  1. Uncouplers of oxidative phosphorylationa.  
    1. Are compounds that allow normal function of electron transport chain without production of ATP.
    2. Uncoupler cause leakage or transport of H+ across the membrane that collapses proton gradient before it can be used for ATP synthesis
    3. Action of Uncoupler is to dissociate oxidation in the respiratory chain from phosphorylation.
    4. Most frequently used Uncoupler is 2,4 – dinitrophenol but other compounds are
      1. CCCP (m- choloro carbonyl cyanide phenyl hydrozone) [CCCP is the most potent uncoupler]
      2. Dinitrocresol
      3. Pentachlorophenol      
      4. Valinomycin            
      5. Calcium
  2. Physiological uncouplers:
    1. Excessive thyroxine hormones                        
    2. Essential fatty acid deficiency
    3. Long chain FA in brown adipose tissue
    4. Unconjugated hyperbilrubinemia
Extra Edge

Brown adipose tissue is the site of "nonshivering. It is found in hibernating and new­born animals and is present in small quantity in hu­mans. Thermogenesis results from the presence of an uncoupling protein, thermogenin, in the inner mito­chondrial membrane. Thermogenin is a most powerful natural Uncouple.

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