Definition of Inhibitors of ETC and oxidative phosphorylation.:
The compounds which inhibit ETC and hence affect oxidative phosphorylation.
These inhibitors bind to the respiratory chain, and not to the enzymes involved in ATP synthesis, which would normally accompany respiration.
Their actions may be mediated by 3 positions that are similar to energy transfer sites I, II, and III.
Examples of Inhibitors:
Rotenone
Electron transport chain inhibitor that is non-toxic.
Obtained from the extracts of roots of tropical plants Derris elliptica.
It binds in Complex I.
Mammals cannot be harmed by this substance since it is poorly absorbed.
Fish are affected by their toxicity.
Pieridine A
Antibiotics are used to treat infections (safer in Humans).
Strains of Streptomyces produce it.
It acts similarly to Rotenone.
Barbiturates:
Coenzyme Q and NADH dehydrogenase are blocked, one of the reason of respiratory failure in barbiturate poisoning.
Antimycin
Streptomyces produces antibiotics called antimycins. Antimycin is an electron transport chain inhibitor.
Site II is inhibited and electrons are prevented from flowing between cytochromes b and c1, preventing ATP synthesis coupled with the formation of a proton gradient.
Dimercaprol
Similar to antimycins, it acts similarly.
Hydrogen sulfide
The disagreeable odor of H2S provides a warning that it is toxic.
Oxidase is inhibited by H2S.
Carbon monoxide
Oxygen and cytochrome oxidase is blocked.
Fer2+ is inhibited as well.
Definition of uncouplers:
An uncoupler is a substance that prevents electron transfer during phosphorylation of ADP.
Compounds that uncouple ATP synthesis from electron transport through the cytochrome system are uncoupling agents.
In this case, oxygen is consumed, but phosphorylation of ADP is inhibited, despite electron transport continuing to function.
Examples of Uncouplers:
2,4-Dinitrophenol
Oxidative phosphorylation is a classic uncoupler.
The substance transports protons across mitochondrial membranes.
This uncoupler prevents mitochondria from forming ATP when electrons are transported from NADH to O2. The protons in the inner mitochondrial membrane are dissipated, resulting in the production of ATP.
In metabolic studies, DNA or other uncouplers are extremely useful because of their specific effect on phosphorylation outside the cell.
Dicoumarol (Vitamin K analogue)
Inhibits the formation of blood clots.
Calcium
Uncoupling can be caused by Ca+2 ions being transported into mitochondria.
Oxidative phosphorylation is tightly coupled to mitochondrial Ca+2 transport.
Uptake of pi is also involved.
Electron transport can occur in mitochondria when calcium is transported there, but energy is required to pump Ca+2 into the mitochondria. ATP cannot be stored as a result.
CCCP (Chloro Carbonyl Cyanide Phenylhydrazone)
Uncoupler with the most activity.
Protons can cross the inner mitochondrial membrane with the help of these lipid-soluble substances.
Physiological uncouplers
Thyroxine hormone is produced in excess
Brown adipose tissue contains long-chain FA
The unconjugated form of hyperbilirubinemia
Valinomycin
It is produced by the streptomyces.
There are four types of residues in this repeating macrocyclic molecule (L-lactate, L-Valine, D-hydroxyisovalerate, and D-Valine).
Reduces the proton gradient by transporting K+ from cytosol to matrix and H+ from matrix to the cytosol.
Commonly Asked Questions:
Define and explain Inhibitors of ETC and oxidative phosphorylation.
What are Uncouplers? Give some examples.