Inhibiting the electron transport chain

There are four “protein complexes” that comprise the electron transport chain (Figure 1). Electrons travel in sequence from their point of entry along the chain. The two points of entry along the electron transport chain are into Complex I and Complex II. NADH is oxidized at Complex I and FADH${}_2$‍ is oxidized at Complex II.

Figure 1. The Electron Transport Chain is depicted by the four complexes embedded in the inner mitochondrial membrane. Barbiturates inhibits Complex I and cyanide inhibits Complex IV.

Flow through the electron transport chain can be adversely affected by a variety of compounds. In Figure 1, the location of inhibition along the electron transport chain is shown for $1)$‍ barbiturates, a type of drug, and $2)$‍ cyanide, a poisonous chemical compound. Other compounds that can inhibit the electron chain include carbon monoxide, certain insecticides, and a fish poison called Antimycin A.

Notably, as shown in Figure 1, only Complexes I, III, and IV pump hydrogen ions into the inter-membrane space as electrons flow through them. Of the three, complexes I and III contribute most to the proton gradient. ATP Synthase depends on this proton gradient to phosphorylate ADP into ATP in the mitochondrial matrix.