Inhibitors of Cytochrome C Oxidase
Azide, Cyanide, and Carbon Monoxide
Or...More Appropriately, Some Inhibitors of Cytochrome c Oxidase
As we've discussed, electron transport is catalyzed by 4 membrane-bound
protein complexes. Complex 4 is Cytochrome c Oxidase. This
complex oxidizes cytochrome c and also reduces O2 to H2O.
Remember that cytochromes have heme cofactors -- this is important in our
discussion of cyanide and azide. Cytochrome c is a soluble
protein and also is a mobile carrier. Other inhibitors of cytochrome
c oxidase will not be discussed here, but are important biologically, such
as sulfide, formate, and nitric oxide.
Cytochrome
Important Links:
An
excellent review of the Respiratory Chain.
Cytochrome
C Oxidase.
Carbon Monoxide
Poisoning -- A discussion of the action of CO in our bodies.
Visit the carbon monoxide headquarters!
Definitions:
Azide: Molecular formula N3-;
inhibits respiration by binding to cytochrome iron atoms.
Carbon
Monoxide: Molecular formula CO; a by-product
of automobiles usage; common pollutant for which home
detectors are available.
Cyanide: Respiration inhibitor. Blocks cytochrome
oxidase (complex 4) and prevents both coupled and uncoupled
respiration with all substrates, including NADH and succinate. Can
cause death within 15 minutes after a
lethal dosage has been received.
Cytochrome C: A mobile carrier, is reduced
as it accepts electrons from the cytochrome b-c1 complex.
As it is
oxidized, cytochrome c conveys its electrons to the cytochrome oxidase
complex. Cytochrome c
is oxidized by reducing cytochrome c1; cytochrome a is oxidized
by reducing cytochrome a3;
cytochrome a3 is oxidized by passing electrons to a molecule
of oxygen
Azide
Surprisingly, little information is available on the internet regarding
azide! What is known is that in electron transport, azide (N3-)
bind to the iron atoms of the oxidized cytochrome, preventing electron
transport. This cytochrome a3-azide complex is difficult
to reduce, unlike the cytochrome a. Azide and cyanide compete for
the iron atom in oxidized cytochrome.
Carbon Monoxide
CO competes with oxygen for binding to the reduced form of cytochrome
c oxidase. Once bound to the cytochrome oxidase, oxygen cannot attach,
and electron transport is stopped. CO is a colorless, tasteless,
non-irritating toxic gas. When inhaled, the toxic gas enters the
bloodstream, depriving the heart and brain of the oxygen necessary to function
correctly. Sensing the body's need for more oxygen, the victim's heart
rate increases to pump more blood to the body's organs. If a person continues
to inhale CO, he or she faces the risk of breathing difficulty, cardiac
trauma, brain damage, coma and even death.
Cyanide
CN-, like azide, binds to the iron atom of oxidized cytochrome,
preventing binding of oxygen. Again, since cytochrome oxidase is
inhibited, oxygen metabolism is prevented and thus so is energy generation.
Cyanide has long been known as a poison, sometimes used in warfare.
As mentioned above, lethal doses cause death in 15 minutes.
Project Links
Back to Project Page
Leah's Page -- Rotenone and Amytal
Rod's Page -- Antimycin
Stan's Page -- Overview of Respiratory Inhibition
Email: rld9881@garnet.fsu.edu
