Ganong's Review of Medical Physiology, 23rd Edition

526 SECTION VI Cardiovascular Physiology
1 × 10 10 RBC
0.3 g hemoglobin
per hour
Bone
marrow
Circulation
3 × 10 13 red blood cells
900 g hemoglobin
Iron
Diet
Amino
acids
FIGURE 32–5 Red cell formation and destruction. RBC, red
blood cells.
hemoglobin (ζ 2 ε 2 ) and Gower 2 hemoglobin (α 2 ε 2 ). There are
two copies of the α globin gene on human chromosome 16. In
addition, there are five globin genes in tandem on chromosome
11 that encode β, γ, and δ globin chains and the two
chains normally found only during fetal life. Switching from
one form of hemoglobin to another during development
seems to be regulated largely by oxygen availability, with relative
hypoxia favoring the production of hemoglobin F both via
direct effects on globin gene expression, as well as up-regulated
production of erythropoietin.
SYNTHESIS OF HEMOGLOBIN
1 × 10 10 RBC
0.3 g hemoglobin
per hour
Tissue
macrophage
system
Bile pigments
in stool, urine
Small amount
of iron
The average normal hemoglobin content of blood is 16 g/dL in
men and 14 g/dL in women, all of it in red cells. In the body of
a 70-kg man, there are about 900 g of hemoglobin, and 0.3 g of
hemoglobin is destroyed and 0.3 g synthesized every hour
CH 3
HC
CH 3
N
N
Fe
CH
Heme
H2C CH2 HC
N
CH
CH= CH2 COOH
CH2 CH3 N
CH2 N
(imidazole) COOH
(imidazole)
Polypeptide chain
CH= CH 2
N
Deoxygenated hemoglobin
CH 3
β
α
+
NH 3
+
NH3 COO −
−
COO
+
NH 3
1 nm
FIGURE 32–6 Diagrammatic representation of a molecule of
hemoglobin A, showing the four subunits. There are two α and two
β polypeptide chains, each containing a heme moiety. These moieties
are represented by the disks. (Reproduced with permission from Harper HA et
al: Physiologische Chemie. Springer, 1975.)
(Figure 32–5). The heme portion of the hemoglobin molecule
is synthesized from glycine and succinyl-CoA (see Clinical
Box 32–2).
CATABOLISM OF HEMOGLOBIN
When old red blood cells are destroyed by tissue macrophages,
the globin portion of the hemoglobin molecule is split off, and
the heme is converted to biliverdin. The enzyme involved is a
subtype of heme oxygenase (see Figure 29–4), and CO is
formed in the process. CO may be an intercellular messenger,
like NO (see Chapters 2 and 3).
HC
CH
M N
M
FIGURE 32–7 Reaction of heme with O 2 . The abbreviations M, V, and P stand for the groups shown on the molecule on the left.
+ O 2
P
M V
N
Fe
N
HC CH
P M
N O 2
Polypeptide chain
Oxyhemoglobin
N
V
β
α