6. PROPERTIES OF FISH HEMOGLOBINS
227
the viscosity of the blood from what it would be if the hemoglobin were
free in the blood plasma. Astonishingly, the appropriate experiment was
not done until very recently when Schmidt-Nielsen and Taylor (1968)
and Cokelet and Meiselman (1968) showed that the viscosity is actually
higher after hemolysis. It appears clear that the primary function of the
erythrocyte membrane is exactly the same as that of all other cell membranes, i.e., to serve as a barrier to the external environment, and to provide for a special controlled internal environment for the optimal function of the cell.
B. Cooperativity : Heme-Heme Interaction and OxygenationLinked Changes in Aggregation of Subunits
The shape of the curve relating degree of oxygenation ( y ) of a blood
hemoglobin to oxygen pressure ( p ) has long been held to be of crucial
importance. Barcroft ( 1928) early argued that an oxygen equilibrium
curve with an S shape was particularly advantageous for animals with
an active metabolism because it resulted in a high “unloading” oxygen
pressure in the tissues relative to the “loading” pressure in gills or lungs.
Hufner’s original description of a hyperbolic curve for human hemoglobin was shown by Bohr to be erroneous (see discussion by Barcroft,
1928). Haldane (1922) suggested that “a man would die on the spot of
asphyxia if the oxygen dissociation curve of his blood were suddenly
altered so as to assume the form which Hiifner supposed it to have in
the living body.” The almost hyperbolic oxygen equilibrium of human
hemoglobin “Kansas” ( Bonaventura and Riggs, 1968) emphasizes that
the significance of the S shape of the equilibrium curve has been exaggerated. Confusion arose because a hyperbolic oxygen equilibrium curve
was thought always to be associated with a high affinity for oxygen as
it is in myoglobin. But this association is by no means always true,
especially in fish hemoglobins. Lamprey hemoglobin, for example, has
a rather low affinity for oxygen. What is necessary to examine, from
the standpoint of oxygen transport adaptation, is not the shape of the
curve per se but the influence of this shape on the actual amount of
oxygen transported.
Oxygcm equilibria are usually plotted in one of three ways: ( l ) ,
y v s . p ; ( 2 ) , y v s . l o g p , o r ( 3 ) , l o g y / ( l -y)vs.logp.Plots ( 2 ) and ( 3 )
arc the most uscful from an analytical standpoint. The slope of the last
plot defincs n in Hills’ equation, y = K p ” / ( 1 + K p ” ) ; n is usually evaluated at y = fh. Any value of n > 1 is taken to indicate the presence of
cooperativity or stabilizing heme-heme interactions between at least
227
the viscosity of the blood from what it would be if the hemoglobin were
free in the blood plasma. Astonishingly, the appropriate experiment was
not done until very recently when Schmidt-Nielsen and Taylor (1968)
and Cokelet and Meiselman (1968) showed that the viscosity is actually
higher after hemolysis. It appears clear that the primary function of the
erythrocyte membrane is exactly the same as that of all other cell membranes, i.e., to serve as a barrier to the external environment, and to provide for a special controlled internal environment for the optimal function of the cell.
B. Cooperativity : Heme-Heme Interaction and OxygenationLinked Changes in Aggregation of Subunits
The shape of the curve relating degree of oxygenation ( y ) of a blood
hemoglobin to oxygen pressure ( p ) has long been held to be of crucial
importance. Barcroft ( 1928) early argued that an oxygen equilibrium
curve with an S shape was particularly advantageous for animals with
an active metabolism because it resulted in a high “unloading” oxygen
pressure in the tissues relative to the “loading” pressure in gills or lungs.
Hufner’s original description of a hyperbolic curve for human hemoglobin was shown by Bohr to be erroneous (see discussion by Barcroft,
1928). Haldane (1922) suggested that “a man would die on the spot of
asphyxia if the oxygen dissociation curve of his blood were suddenly
altered so as to assume the form which Hiifner supposed it to have in
the living body.” The almost hyperbolic oxygen equilibrium of human
hemoglobin “Kansas” ( Bonaventura and Riggs, 1968) emphasizes that
the significance of the S shape of the equilibrium curve has been exaggerated. Confusion arose because a hyperbolic oxygen equilibrium curve
was thought always to be associated with a high affinity for oxygen as
it is in myoglobin. But this association is by no means always true,
especially in fish hemoglobins. Lamprey hemoglobin, for example, has
a rather low affinity for oxygen. What is necessary to examine, from
the standpoint of oxygen transport adaptation, is not the shape of the
curve per se but the influence of this shape on the actual amount of
oxygen transported.
Oxygcm equilibria are usually plotted in one of three ways: ( l ) ,
y v s . p ; ( 2 ) , y v s . l o g p , o r ( 3 ) , l o g y / ( l -y)vs.logp.Plots ( 2 ) and ( 3 )
arc the most uscful from an analytical standpoint. The slope of the last
plot defincs n in Hills’ equation, y = K p ” / ( 1 + K p ” ) ; n is usually evaluated at y = fh. Any value of n > 1 is taken to indicate the presence of
cooperativity or stabilizing heme-heme interactions between at least