Electron transport chain (ETC) and biological oxidation

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Some basic concepts
  • Oxidation means loss of electrons
  • Reduction means gain of electrons
  • The compound which donates electron is said to be oxidized; while, the compound which accepts electrons is said to be reduced.

1. Introduction to ETC
  • The biomolecules like carbohydrates, fatty acids, and amino acids undergo a series of metabolic reactions forming a wide variety of intermediates.
  • These intermediates get oxidized by donating electrons to the coenzyme NAD+ and FAD leading to their reduction into NADH and FADH2 respectively.
  • Further the reduced coenzymes (NADH and FADH2) pass through ETC, donating electrons to various enzyme complexes and finally reduce oxygen to water with the formation of ATP.
  • ETC is constituted by five enzyme complexes (made up of group of proteins) located on inner mitochondrial membrane.
2. Five enzyme complexes of ETC
  • Complex I: NADH CoQ reductase or NADH dehydrogenase
  • Complex ll: Succinate CoQ reductase or Succinate dehydrogenase
  • Complex lll: CoQ-cytochrome C reductase or Ubiquinone cyto. C oxidoreductase
  • Complex lV: Cytochrome oxidase
  • Complex V: ATP synthase
Complex I to IV serve as carrier of electrons.
Complex V is responsible for ATP synthesis (hence called phosphorylation unit or ATP synthase).
There are some other electron carriers which are also involved in ETC, like coenzyme Q (Co. Q), cytochrome c (cyto. c), etc.
The following figure depicts the electron transport system (or chain) which shows the sequential flow of electrons from one carrier to another.
It should be noted that, if the substrate is NADH, then electrons are transferred to complex I; if it is Succinate (FADH) , then  electrons are transferred to complex II.
That is why energy generated from NADH is more as compared to FADH (explained in biological oxidation).
3. Biological oxidation (Oxidative phosphorylation)
  • Oxidation of NADH and FADH2 with subsequent phosphorylation of ADP to liberate energy in the form of ATP is called biological oxidation.
  • Occurs at complex V of ETC
  • The transfer of electrons through ETC is accompanied by movement of protons (H+) from mitochondrial matrix to inter-membranal space
  • This generates difference in the pH (chemical gradient) and charge (electrical gradient) in between the mitochondrial matrix and inter-membranal space
    • Difference in pH (chemical gradient): As protons are acidic; their movement inside inter-membranal space is accompanied by increase in acidity. Conversely, the pH inside the matrix become more basic due to loss of acidic proton.
    • Difference in charge (electrical gradient): As protons are positively charged; their movement inside inter-membranal space is accompanied by increase in electropositivity. Conversely, the charge inside the matrix become more electronegative due to loss of positively charged proton.
  • In order to maintain homeostasis; protons have to come back again into the matrix.
  • Since, the inner mitochondrial membrane is impermeable to protons, they can re-enter the matrix only through proton-specific channels in complex V
  • This movement of proton through complex V provide energy to convert (phosphorylate) ADP into ATP
  • Now, as explained earlier, if the substrate is NADH, then electrons are transferred to coenzyme Q via complex I; and at the same time 4 protons are transferred to inter-membrane space.
  • However, if substrate is succinate (FADH); electrons are transferred to coenzyme Q via complex II; no protons are transferred during this.
  • Thus, total proton transfer will be 10 (in case of NADH) and 6 (in case of FADH).
  • That is why energy generated from NADH is more as compared to FADH. 

4. Agents that interfere with ETC or biological oxidation

1). Inhibitors of ETS 
Compounds
Mode of action
Cyanide, Carbon mono oxide
Inhibit cytochrome oxidase
Antimycin A
Blocks electron tranfer from cyt. b to c1
Rotenone, Amytal, Piericidin A
Prevent electron transfer from Fe-S to ubiquinone

2). Inhibitors of ATP synthase 
Oligomycin, Aurovertin
Binds with the enzyme ATPase synthase ==> blocks the proton channel ==> ultimately ETC stops

3). Uncouplers: DNP (2,4-Dinitrophenol), dinitrocresol, pentachlorophenol
ETC is coupled with the oxidative phosphorylation. The compounds which uncouple this, are called as Uncouplers. They increase the permeability of inner mitochondrial membrane to protons ==> protons will be coming back to matrix through membrane ==> ATP synthesis does not occur.

4). Other inhibitors: Atractyloside
A plant toxin ==> blocks the supply of ADP ==> prevent phosphorylation of ADP into ATP.

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