CLINICAL CASES
149
3.
Be familiar with the biochemical process by which the therapy for
cyanide poisoning works. (Nitrates convert the hemoglobin to methemo-
globin which has a higher affinity for cyanide and promotes dissociation
from cytochrome oxidase. Thiosulfate reacts with cyanide which is
slowly released from cyanomethemoglobin to form thiocyanate. Oxygen
reverses the binding of cyanide to cytochrome oxidase.)
4.
Recognize other ETC sites and agents of inhibition.
D efinitions
Oxidative phosphorylation: The mitochondrial process whereby electrons
from NADH or reduced flavin bound in enzymes are transferred down
the electron transport chain to oxygen forming water and providing
energy through the formation of an hydrogen ion gradient across the
inner mitochondrial membrane. The hydrogen ion gradient is used to
drive the formation of ATP from ADP and inorganic phosphate (Pi). This
process is also called
coupled oxidative phosphorylation
to emphasize
that ATP formation from ADP and Pi is coupled to and linked with elec-
tron transport such that inhibition of one also inhibits the other.
Hydrogen ion gradient: A situation developed across the inner mitochon-
drial membrane wherein the concentration of hydrogen ions outside the
mitochondrion is higher than the concentration inside. Hydrogen ions
are extruded from the mitochondrion by the transfer of electrons from
complex I to coenzyme Q, from coenzyme Q to complex III, and from
complex III to complex IV. The gradient is discharged by ATP synthase,
which admits hydrogen ions into the mitochondrion thereby driving the
phosphorylation of ADP by Pi.
Electron transport chain: Present in the mitochondrial membrane, this
linear array of redox active electron carriers consists of NADH dehy-
drogenase, coenzyme Q, cytochrome c reductase, cytochrome c, and
cytochrome oxidase as well as ancillary iron sulfur proteins. The elec-
tron carriers are arrayed in order of decreasing reduction potential such
that the last carrier has the most positive reduction potential and trans-
fers electrons to oxygen.
Reduction potential: The tendency of an electron carrier to give up elec-
trons, stated in electron volts, is called reduction potential. In any
reduction-oxidation reaction electrons flow from the species with the
more negative reduction potential to the more positive reduction
potential.
Cytochrome: A heme (protoporphyrin IX) containing electron transfer
protein. Some heme moieties are covalently attached to the protein
components (cytochrome c), whereas others have isoprenoid side chains
(cytochromes a and a3).
Iron sulfur proteins: These carry one electron and contain centers that
chelate iron with organic and inorganic sulfur. Some centers contain a
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