Biology Reference
In-Depth Information
1.00
Lowest [HEME] = 4
×
10
−
8
M
.75
f
2
.50
.25
.00
.00
.25
.50
.75
1.00
Y
FIGURE 7-6.
The fraction of dimeric hemoglobin present in solution as a function of the fractional saturation of
the oxygenation linked 2ab $ a
2
b
2
subunit assembly reaction. The upper curve corresponds to the
lowest hemoglobin concentration of 4 10
8
M hemoglobin monomers while the lower curve is for
4 10
4
M hemoglobin monomers.
(Reprinted with permission from Mills, F.C., Johnson, M.L., and Ackers, G.K. [1976]. Oxygenation-
linked subunit interactions in human hemoglobin: Experimental studies on the concentration
dependence of oxygenation curves. Biochemistry, 15, 5350-5362.
#
1976 The American Chemical
Society.)
where [Hg] is the total molar concentration of hemoglobin (monomers),
[O
2
] is the molar concentration of unbound O
2
, the constant
0
K
2
is the
equilibrium constant for dimer-tetramer assembly 2
ab $ a
2
b
2
, and:
2
X
2
¼
1
þ
K
21
½
O
2
þ
K
22
½
O
2
2
X
2
0
¼
K
21
½
O
2
þ
2K
22
½
O
2
(7-19)
2
3
4
X
4
¼
1
þ
K
41
½
O
2
þ
K
42
½
O
2
þ
K
43
½
O
2
þ
K
44
½
O
2
2
3
4
X
4
0
¼
K
41
½
O
2
þ
2K
42
½
O
2
þ
3K
43
½
O
2
þ
4K
44
½
O
2
:
The quantities
X
4
in Eqs. (7-18) and (7-19) are sometimes referred
to as binding polynomials. The quantities
X
2
and
X
2
' and
X
4
' in Eqs. (7-18) and
(7-19) are related to
X
4
, as we shall explore later. Although
deriving Eq. (7-18) is beyond the scope of this textbook, we shall use
binding polynomials to derive Adair's equation [Eq. (7-16)].
X
2
and
As mentioned, Eq. (7-18) could be thought of as the appropriately
weighted average of the Adair-binding equations for the dimeric
hemoglobin species (the 2i subscripts) and the tetrameric hemoglobin
species (the 4i subscripts). The only assumption required for the
derivation of Eqs. (7-18) and (7-19) is the reaction scheme depicted in
Figure 7-5. Thus, Eqs. (7-18) and (7-19) apply to normal human
hemoglobin, which exists in solution as
ab
dimers that undergo
a reversible association reaction to form (
)
2
tetramers. Human
hemoglobin dimers bind O
2
with higher affinities than tetramers. As the
concentration of hemoglobin decreases, the fraction of dimers present
increases (see Figure 7-6), and the hemoglobin concentration-dependent
ab
