Back to Biochemistry Lesson preview
Biochemistry Biological Oxidation

Inhibitors and Uncouplers of ETC

Topic overview

Start with the big picture

The electron transport chain supports ATP synthesis through oxidative phosphorylation in the inner mitochondrial membrane. Inhibitors block electron flow at specific complexes: examples include rotenone at Complex I, antimycin A at Complex III, and cyanide at Complex IV. Oligomycin instead inhibits the Fo channel of ATP synthase, while atractyloside and bongkrekic acid block adenine nucleotide exchange. These disruptions reduce ATP synthesis and oxygen consumption. Uncouplers, by contrast, dissipate the proton gradient, so electron flow and oxygen consumption rise while ATP output falls to zero. Examples include chemical uncouplers such as 2,4-DNP, the physiological uncoupler thermogenin in brown adipose tissue, and ionophores. The lesson’s central comparison is that inhibitors and uncouplers both prevent ATP synthesis but have opposite effects on oxygen use.

Learning objectives

What you'll learn

  • Distinguish ETC inhibitors from uncouplers by their effects on electron flow and oxygen consumption.
  • Identify inhibitor examples acting at Complexes I–IV.
  • Explain how oligomycin and adenine nucleotide translocase blockers affect ATP production.
  • Describe how uncouplers dissipate the proton gradient and identify major examples.
  • Compare physiological, chemical, and ionophore uncouplers.
Ready for the complete lesson?

Continue your study

Work through the complete notes and reinforce the topic with the study tools available in the full lesson.

PharmaProLearn

Excel Beyond Limits