Page 289 - Color Atlas of Biochemistry

280 Tissues and organs
Hemoglobin
The most important task of the red blood cells
(erythrocytes) is to transport molecular oxy-
gen (O 2 ) from the lungs into the tissues, and form leads to a local conformational change
carbon dioxide (CO 2 )from the tissues back
into the lungs. To achieve this, the higher
organisms require a special transport system,
since O 2 is poorly soluble in water. For exam- to the higher–af nity R form. This coopera-
ple, only around 3.2 mL O 2 is soluble in 1 L
blood plasma. By contrast, the protein hemo-
globin (Hb), contained in the erythrocytes,
can bind a maximum of 220 mL O 2 per
liter—70 times the physically soluble amount.
The Hb content of blood, at 140–180 g L –1
in men and 120–160 g L –1 in women, is
twice as high as that of the plasma proteins
–1
(50–80 g L ). Hb is therefore also responsi-
ble for the majority of the blood proteins’ pH
buffer capacity (see p. 288).
A. Hemoglobin: structure
In adults, hemoglobin (HbA;see below) is a
heterotetramer consisting of two α-chains and
two β-chains, each with masses of 16 kDa.
The α-and β-chains have different sequences,
but are similarly folded. Some 80% of the
amino acid residues form D-helices, which
are identified using the letters A–H.
Each subunit carries a heme group (for-
mula on p. 106), with a central bivalent iron
ion.When O 2 binds to the heme iron
(Oxygenation of Hb) and when O 2 is released
(Deoxygenation), the oxidation stage of the
iron does not change. Oxidation of Fe 2+ to
Fe 3+ only occurs occasionally. The oxidized
form, methemoglobin, is then no longer able
to bind O 2 . The proportion of Met-Hb is kept
low by reduction (see p. 284) and usually
amounts to only 1–2%.
Four of the six coordination sites of the iron
in hemoglobin areoccupied by thenitrogen
atoms of the pyrrol rings, and another is oc-
cupied by a histidine residue of the globin
(the proximal histidine). The iron’s sixth site
is coordinated withoxygeninoxyhemoglobin
and with H 2 Oin deoxyhemoglobin.
B. Hemoglobin: allosteric effects
Like aspartate carbamoyltransferase (see
p. 116), Hb can exist in two different states
(conformations), known as the T form and
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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the R form. The Tform (for tense; left) and
has a much lower O 2 af nity than the R form
(for relaxed; right).
Binding of O 2 to one of the subunits of the T
that weakens the association between the
subunits. Increasing O 2 partial pressure thus
means that more and more molecules convert
tive interaction between the subunits in-
creases the O 2 af nity of Hb with increasing
O 2 concentrations—i. e., the O 2 saturation
curve is sigmoidal (see p. 282).
Various allosteric effectors influence the
equilibrium between the T and R forms and
thereby regulate the O 2 binding behavior of
hemoglobin (yellow arrows). The most impor-
+
tant effectors are CO 2 ,H , and 2,3-bisphospho-
glycerate (see p. 282).
Further information
As mentioned above, hemoglobin in adults
consists of two α-and two β-chains. In addi-
tiontothis mainform (HbA 1 , α 2 β 2 ), adult
blood also contains small amounts of a second
form with a higher O 2 af nity in which the β-
chains are replaced by δ-chains (HbA 2 , α 2 δ 2 ).
Two other forms occur during embryonic and
fetal development. In the first three months,
embryonic hemoglobins are formed, with the
structure ζ 2 ε 2 and α 2 ε 2 .Up to the time of
birth, fetal hemoglobin then predominates
(HbF, α 2 γ 2 ), and it is gradually replaced by
HbA during the first few months of life. Em-
bryonic and fetal hemoglobins have higher O 2
af nities than HbA, as they have to take up
oxygen from the maternal circulation.