H b(Fe+2)0 2 + N 0 2-
M etHb(Fe+3)O H + N 0 3-
M etHb(Fe+3)O H + cyt a/a3(Fe+3)-C N ---------------►
cyt a/a3(Fe +3) + M etHb(Fe+3)-C N -
M etHb(Fe+3)-C N - + S 20 3-2
S C N - + S 0 3'2 + M etHb(Fe+3)OH
Figure 16-3. Strategy for reversal of cyanide binding to cytochrome oxidase
(cyt a/a3 Fe3+).
[met-HbOH(Fe3+)], another competitor for cyanide binding (Figure 16-3). The
cyanide adduct of methemoglobin is formed releasing cytochrome oxidase in the
Fe3+ form ready to bind oxygen and disinhibit the electron transport chain. To
remove the cyanide adduct in a nontoxic fashion, thiosulfate ion is administered.
The mitochondrial enzyme rhodanese catalyzes the conversion of cyanide and
thiosulfate to thiocyanate and sulfite. Thiocyanate is incapable of inhibiting
cytochrome oxidase and is excreted. The methemoglobin can be reconverted to
oxyhemoglobin by NADH and methemoglobin reductase.
Other sites of the electron transport chain can be targets of inhibitors based
on similarity in structure to enzyme components or to substrates of the various
components. For instance, the fish poison rotenone resembles the isoallox-
azine ring of the FMN cofactor of complex I, the NADH CoQ reductase.
Rotenone binds the enzyme quite avidly and prevents transfer of electrons
from NADH to coenzyme Q through the iron sulfur centers and thus inhibits
oxidation of NADH and subsequent reduction of oxygen to water. On the other
hand, carbon monoxide resembles molecular oxygen and binds with a higher
affinity than oxygen to complex IV, the cytochrome oxidase component,
inhibiting transfer of electrons to oxygen.
C O M P R E H E N SIO N Q U E ST IO N S
A 16-month-old girl was found to have ingested approimately 30 mL of an
acetonitrile-based cosmetic nail remover when she vomited 15 minutes
postingestion. The poison control center was contacted, but no treatment was
recommended because it was confused with an acetone-based nail polish
remover. The child was put to bed at her normal time, which was 2 hours
postingestion. Respiratory distress developed sometime after the child was put
to bed, and she was found dead the next morning.
[16.1] Inhibition of which of the following enzymes was the most likely cause
of this child’s death?
A. Cytochrome c reductase
B. Cytochrome oxidase
C. Coenzyme Q reductase
D. NADH dehydrogenase
E. Succinate dehydrogenase