Respiratory poisons

A wide variety of different compounds act as respiratory poisons, and inhibit the oxidation of metabolic fuels linked to the phosphorylation of ADP to ATP.

• Cyanide and carbon monoxide, well known poisons.
• Sodium azide - another well-known poison
• Antimycin - one of a family of antibiotics produced by Streptomyces spp., some of which are used as fungicides against fungi that are parasitic on rice.
• Amytal (amobarbital) - a barbituric acid derivative widely used as a sedative or hypnotic drug.
• Rotenone - the main insecticidal compound in derris powder, extracted from the root of the leguminous plant Lonchocarpus nicou.
• Oligomycin - one of a family of antibiotics produced by Streptomyces spp., which is of little or no therapeutic use.
• Atractyloside - a toxic alkaloid from the rhizomes of the Mediterranean thistle Atractylis gummiferra. It competes with ADP for binding to the adenine nucleotide transporter.
• Bongkrekic acid - a toxic antibiotic formed by Pseudomonas cocovenans growing on coconut. It anchors the adenine nucleotide transporter at the inner face of the membrane, so that ATP cannot be transported out, nor ADP in.

You will be able to perform experiments with several of these compounds, and you should be able to deduce how they act from your results.

... and a respiratory stimulant

2,4-dinitrophenol is a weak acid; the ionised form is water-soluble, whereas the protonated (unionised) form is lipid-soluble and will diffuse through membranes. It can thus act to transport protons from one side of the mitochondrial membrane to the other, as can a variety of weak acids.

Consumption of dinitrophenol leads to an increased metabolic rate, high oxygen consumption and a high body temperature. As you perform experiments with dinitrophenol added to your mitochondrial preparation you should be able to deduce how its acts to stimulate substrate oxidation.