Inhibitors ETC and oxidative phosphorylation/Uncouplers

Inhibitors ETC

As much as possible, 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 loci that are similar to energy transfer sites I, II, and III. The following compounds inhibit electron transport.

Rotenone

• Electron transport chain inhibitor that is non-toxic.
• Extracts of roots of tropical plants Derris elliptica and Lonchoncarpus you provide these compounds.
• Between the Fe-S protein and Ubiquinone, 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.
• Strains of Streptomyces produce it.
• It acts similarly to Rotenone.

Barbiturates (Amytal, Seconal)

• Coenzyme Q and NADH dehydrogenase are blocked.

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.
• An antimycin A concentration of 0.07 micromoles per gram of mitochondrial protein is effective.

Dimercaprol

• Similar to antimycins, it acts similarly.

Azide

• The cytochrome oxidase complex cannot exchange electrons with oxygen due to the presence of azide.
• As this carrier consists of a ferric form (Fe3+), azide reacts with it.

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.

Oxidative phosphorylation/uncouplers

The definition of 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.

Some uncoupling agents are listed below.

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 Phenyl hydrazone)

• Uncoupler with the most activity.
• Protons can cross the inner mitochondrial membrane with the help of these lipid-soluble substances.

Physiological uncouplers

• Thyroxin hormone is produced in excess
• Deficiency of EFC is seen
• Brown adipose tissue contains long-chain FA
• The unconjugated form of hyperbilirubinemia

Valinomycin

• An ionophore of oxidative phosphorylation, such as this one.
• It is produced by the streptomyces.
• There are four types of residues in this repeating macrocyclic molecule (L-lactate, L-Valine, D-hydroxyisovalarate, and D-Valine) taken three times each.
• Reduces the proton gradient by transporting K+ from cytosol to matrix and H+ from matrix to the cytosol.

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