Methemoglobin: Hemoglobin in which the iron atom has been oxidized to
the ferric (+3) state and is therefore incapable of binding O2.
Carboxyhemoglobin: Hemoglobin that has bound CO is called carboxy-
hemoglobin. Carbon monoxide binds to hemoglobin with 200 times the
affinity of O2.
Carbon monoxide poisoning has two primary effects: interference with O2
transport to tissues and interference with the interaction of O2 with
cytochromes, especially the cytochromes in the electron transport chain.
The transport of O2 from the lungs to peripheral tissues and central organs
is mediated by hemoglobin, a four subunit (2a- and 2P-globin chains) protein.
Hemoglobin has four active sites enabling it to bind four molecules of O2 per
molecule in the lungs for transport by the red blood cell to distant tissues,
where O2 is released for direct use or for binding to other proteins such as mus-
cle myoglobin. Although the globin portion of myoglobin is similar to hemoglo-
bin, it acts as a monomer with only one O2-binding site. The four O2-binding
sites of hemoglobin exhibit positive cooperativity in binding O2. The binding
of the first molecule of O2 occurs with a modest affinity but causes a confor-
mational change that enhances hemoglobin’s binding affinity for a second
molecule of O2. Likewise, the binding of the second enhances the binding
affinity for the third and the third, for the fourth molecule of O2.
Carbon monoxide competes with O2 for the four hemoglobin-binding sites,
but CO binds 220 times more avidly to hemoglobin than O2. Moreover, CO
shows the same positive cooperativity that O2 does. These features combine
in favor of CO binding. Atmospheric air is 21 percent O2, whereas the usual
CO concentration is 0.1 parts per million (ppm). In heavy traffic, the CO concen-
tration may be 115 ppm. A nearly tenfold increase, up to 1000 ppm (0.1 percent)
carbon monoxide, results in a 50 percent carboxyhemoglobinemia. Although the
reduction in O2-transport capacity is proportional to the proportion of carboxy-
hemoglobin [COHb], the amount of O2 available to tissues for use is further
reduced by the inhibitory effect of COHb on the dissociation of oxyhemo-
globin. Although the average person may show no symptoms at 10 percent
of hemoglobin in the form of COHb, any complication such as anemia that
reduces O2 transport capacity may exhibit symptoms at a lower percentage of
carboxyhemoglobin. At 10 to 20 percent COHb, headache and dilation of
cutaneous blood vessels may appear, whereas at 20 to 30 percent,
headaches may become stronger. At 30 to 40 percent carboxyhemoglobin,
serious headache, dizziness, disorientation, nausea, and vomiting occur.
At levels exceeding 40 percent, patients usually collapse and have worsen-
ing of other symptoms. These symptoms reflect failure of O2 transport as well
as direct inhibition of O2-binding cytochromes such as cytochrome oxidase or
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