Much information about the respiratory chain has been obtained by the use of inhibitors, and, conversely, this has provided knowledge about the mechanism of action of several poisons (Figure 1). They may be classified as inhibitors of the respiratory chain, inhibitors of oxidative phosphorylation, or uncouplers of oxidative phosphorylation.

Fig1. Sites of inhibition (⊖) of the respiratory chain by specific drugs, chemicals, and antibiotics. (BAL, dimercaprol; TTFA, an Fe-chelating agent. )

Barbiturates such as amobarbital inhibit electron trans port via Complex I by blocking the transfer from Fe-S to Q. At sufficient dosage, they are fatal. Antimycin A and dimercaprol inhibit the respiratory chain at Complex III. The classic poisonsH₂S,carbon monoxide, and cyanide inhibit Complex IV and can therefore totally arrest respiration. Malonate is a competitive inhibitor of Complex II.

Atractyloside inhibits oxidative phosphorylation by inhibiting the transporter of ADP into and ATP out of the mitochondrion (Figure 2). The antibiotic oligomycin completely blocks oxidation and phosphorylation by blocking the flow of protons through ATP synthase.

Fig2. Transporter systems in the inner mitochondrial membrane. ➀Phosphate transporter, ➁pyruvate symport, ➂dicarboxylate transporter, ➃ tricarboxylate transporter, ➄α-ketoglutarate transporter, ➅ adenine nucleotide transporter. N-Ethylmaleimide, hydroxycinnamate, and atractyloside inhibit (⊖) the indicated systems. Also present (but not shown) are transporter systems for glutamate/aspartate , glutamine, ornithine, neutral amino acids, and carnitine .

Uncouplers dissociate oxidation in the respiratory chain from phosphorylation . These compounds are toxic, causing respiration to become uncontrolled, since the rate is no longer limited by the concentration of ADP or Pi . The uncoupler that has been used most frequently in studies of the respiratory chain is 2,4-dinitrophenol, but other com pounds act in a similar manner. Thermogenin (or uncoupling protein 1 [UCP1]) is a physiologic uncoupler found in brown adipose tissue that functions to generate body heat, particularly for the newborn and during hibernation in animals .

مواضيع ذات صلة

Overview of Substrate Metabolism in Fasting & Feasting

The selective permeability of the inner mitochondrial membrane necessitates exchange transporters

The Respiratory Chain Provides Most Of The Energy Captured During Catabolism

Electron Transport Via The Respiratory Chain Creates A Proton Gradient Which Drives The Synthesis of ATP

The Respiratory Chain Oxidizes Reducing Equivalents & Acts as A Proton Pump

دورة الخلية وتخليق الدنا Cell Cycle & DNA Synthesis

Oxygenases Catalyze The Direct Transfer & Incorporation of Oxygen Into A Substrate Molecule

Hydroperoxidases Use Hydrogen Peroxide or an Organic Peroxide as Substrate

اضطرابات استقلاب النوكليوتيدات البيريميدينية

اضطرابات استقلاب النكليوتيدات البورينية

تخليق النوكليوتيدات منقوصة الاكسجين ( dNTPs )

تقويض النوكليوتيدات البيريميدينية