Ganong's Review of Medical Physiology, 23rd Edition

526
SECTION VI
Cardiovascular Physiology

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 chromo-
some 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 rela-
tive hypoxia favoring the production of hemoglobin F both via
direct effects on globin gene expression, as well as up-regulat-
ed production of erythropoietin.

SYNTHESIS OF HEMOGLOBIN

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

(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).

FIGURE 32–5
Red cell formation and destruction.
RBC, red
blood cells.

Circulation

3 × 1013 red blood cells

900 g hemoglobin

1 × 1010 RBC

0.3 g hemoglobin

per hour

1 × 1010 RBC

0.3 g hemoglobin

per hour

Tissue

macrophage

system

Bone

marrow

Iron

Diet

Amino

acids

Bile pigments

in stool, urine

Small amount

of iron

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.)

1 nm

COO

+

−

COO

−

NH 3

+

NH 3

+

NH 3

α

β

α

β

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.

N

HC CH

N

N

NN

HC

H 2 C

CH

N

CH 3

CH 3

CH 2 CH 3

CH 2

COOH

CH 3

CH=CH 2

CH=CH 2

CH 2

COOH

Fe

Polypeptide chain

(imidazole)

Heme

(imidazole)

Deoxygenated hemoglobin

N

HC CH

N

N

NO 2

+ O 2

HC CH

N

MV

PM

MM

P V

Fe

Polypeptide chain

Oxyhemoglobin