Biochemistry · Enzyme
Cytochrome c oxidase (complex IV) !
Cytochrome c oxidase is the last complex of the chain: it hands the electrons to oxygen, makes water and pumps protons.
Updated 2026-11-01
Loading the 3D model…
Key facts
- 4 cytochrome c (Fe²⁺) + O₂ + 8 H⁺ (matrix) → 4 cytochrome c (Fe³⁺) + 2 H₂O + 4 H⁺ pumped.
- Metal centres in order: CuA → heme a → heme a₃–CuB, where O₂ binds and is reduced.
- It binds O₂ tightly and releases no toxic intermediates: that is why almost all the oxygen we breathe ends up as water.
- Cyanide, CO, azide and H₂S bind heme a₃ and block it.
- Also called
- Complex IV, Cytochrome aa₃
- EC number
- 7.1.1.9
- Genes
- MT-CO1, MT-CO2, MT-CO3…; SURF1
- Structure (PDB)
- 3AG4
Regulation
- Nitric oxide competes with O₂ and slows it physiologically.
- Subunit isoforms vary with tissue and oxygen level.
Inhibitors and toxins
- Cyanide
- Carbon monoxide
- Azide
- Hydrogen sulfide (H₂S)
Clinical notes
- Cyanide poisoning blocks it within minutes: severe lactic acidosis with highly oxygenated venous blood.
- CO, besides occupying hemoglobin, binds it and inhibits cellular respiration.
- Variants in SURF1 and other assembly genes cause complex IV deficiency with Leigh syndrome.
- In a muscle biopsy, fibres without cytochrome c oxidase activity (COX-negative) suggest mitochondrial disease.
Pathways
Related conditions
Related
- Cytochrome c
- Complex III (cytochrome bc₁)
- ATP synthase (complex V)
- Hemoglobin and 2,3-BPG
- Chemiosmosis and the proton gradient
Test yourself
Think of the answer, then tap the question to see it.
Where does cyanide bind in the respiratory chain?
To the heme a₃ iron of cytochrome c oxidase (complex IV): the chain stops and O₂ is not used.
Which metals does cytochrome c oxidase contain?
Copper (CuA and CuB) and iron in hemes a and a₃.
How many electrons does complex IV need to reduce one O₂ molecule?
Four, received from four cytochrome c molecules; two water molecules are formed.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: MT-CO1: Cytochrome c oxidase subunit 1 (human) (UniProt, 2026); 3AG4: Bovine Heart Cytochrome c Oxidase in the Cyanide Ion-bound Fully Reduced State at 100 K (RCSB Protein Data Bank, 2026); SURF1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.