Textbook - BIOLOGICAL CHEMISTRY - Gubsky Yu.I. - 2000

Chapter II. GENERAL PRINCIPLES OF METABOLISM

CHAPTER 9. BIOENERGETIC PROCESSES: ELECTRON TRANSPORT; OXIDATIVE PHOSPHORYLATION IN MITOCHONDRIA

9.5. INHIBITORS OF ELECTRON TRANSPORT AND OXIDATIVE PHOSPHORYLATION IN MITOCHONDRIA

Certain chemical compounds can specifically disrupt electron transport (electron transport inhibitors) and Oxidative Phosphorylation (inhibitors and uncouplers of oxidative phosphorylation) in Cell/35.html">Mitochondria. These compounds interact with specific Components of the Respiratory Chain or oxidative phosphorylation systems, disrupting their biochemical Functions.

Class="center">Electron transport inhibitors

Compounds of this class disrupt the functioning of the mitochondrial respiratory chain by binding to individual enzyme Proteins or Coenzymes that are directly involved in The transfer of electrons from Biological Oxidation substrates to O₂. When introduced into the human or animal body, these substances act as cellular poisons, causing tissue Hypoxia.

Rotenone is an inhibitor of electron transport through the NADH-coenzyme Q reductase complex. Rotenone is used as an insecticide.

Amobarbital (amytal) and its structural analogue secobarbital (seconal). These barbituric acid derivatives (barbiturates) are used in pharmacology as sleeping AIDS. At the same time, barbiturates, much like rotenone, are active inhibitors of cellular Respiration, blocking electron transport at the level of NADH-coenzyme Q reductase.

Piericidin A is an antibiotic that also blocks the NADH-coenzyme Q reductase complex through competitive interaction with ubiquinone.

Antimycin A is an antibiotic that blocks the mitochondrial respiratory chain at the level of electron transfer via complex III (cytochrome b — cytochrome C₁).

Cyanides (CN^- ions) are potent cellular poisons that inhibit electron transport at the terminal segment of the mitochondrial respiratory chain (in the cytochrome c oxidase complex). CN^- ions form complexes with the ferric (Fe³⁺) form of cytochrome c oxidase heme molecules, blocking their reduction to the ferrous (Fe²⁺) form.

Carbon monoxide (CO) inhibits cytochrome c oxidase by binding to the heme site that interacts with the oxygen molecule.

Inhibitors of oxidative phosphorylation

Inhibitors of oxidative phosphorylation block both substrate oxidation and ADP phosphorylation in mitochondria.

Oligomycin is an antibiotic that counteracts both the phosphorylation of ADP to ATP and The stimulation of O₂ consumption observed upon The addition of ADP to mitochondria (the "Respiratory Control" phenomenon). The Mechanism of oligomycin action involves the inhibition of ATP synthase function.

Uncouplers of oxidative phosphorylation

Compounds of this class induce "uncontrolled" mitochondrial respiration that does not depend on the functioning of the ADP phosphorylation system. In the presence of uncouplers, active O₂ consumption is observed despite a decreased rate (or absence) of ATP generation from ADP and P_i. According to the chemiosmotic theory, uncouplers cause the membrane to lose its proton potential — the driving force for the generation of high-energy ATP bonds.

Uncouplers of oxidative phosphorylation include:

- 2,4-dinitrophenol and chemically related compounds (dinitrocresol, pentachlorophenol);

- FCCP (carbonyl cyanide p-trifluoromethoxyphenylhydrazone) — a compound with a specific activity 100 times that of 2,4-dinitrophenol.

THYROID Hormones (thyroxine, triiodothyronine) also have The ability to uncouple respiration and oxidative phosphorylation in mitochondria.

The sites of Introduction/43.html">Action of Certain electron transport inhibitors, as well as inhibitors and uncouplers of oxidative phosphorylation, are shown in the diagram.

Impaired ATP synthesis is observed when the human or animal body is exposed to numerous pathogenic factors of chemical (natural and synthetic toxins), biological, and physical (ionizing radiation) origin. These factors cause the Uncoupling of respiration and oxidative phosphorylation by disrupting the ability to generate and maintain a proton potential across the coupling membranes of mitochondria.