654
CHAPTER 28
Hemoglobin
□
g
(3
G lu c o se 6 -p h o sp h a te
l
0
с—о—
ро
Г
н—с—он
1
"
нр—о—Р0
3
1 ,3 B isp h o sp h o g ly cera te
(1,3-DPG )
2-P G
Р and free 2,3-D P G
COO"
B isp h o sp h o g ly cera te m u ta se
3 -P G cofactor
H—C-
I
H ,c -
-o— po;
-o—po!
2 ,3 B isp h o sp h o g ly cera te
(2,3-DPG )
(3-PG)
P h o sp h o g ly c era te m u ta se
(2,3-D P G is a n en zy m e-b o u n d
in term ed iate/cofactor)
COO"
— — —
L actate
h—c —o—po;
нр—OH
2 -P h o sp h o g ly cer a te
(2-P G )
FIGURE 28-9
Formation of 2,3-bisphosphogIycerate (2,3-DPG) in erythrocytes. Formation of 2,3-DPG occurs as a shunt from the
main pathway of glycolysis, and free energy is used that otherwise would have been employed in the formation of ATP.
© , Positive allosteric modifier; © , negative allosteric modifier; Pj, inorganic phosphate.
cells is higher than that in old red cells. This may
reflect a general change in activity of
bisphosphoglycerate mutase and phosphatase. Since
erythrocytes are unable to synthesize proteins,
inactivated enzymes cannot be replaced.
4. There may also be genetic control over 2,3-DPG
levels. The ATP concentration in erythrocytes is under
hereditary control, and in hooded rats, levels of ATP
and 2,3-DPG appear to be genetically influenced.
However, this finding may be of no importance in
producing rapid, short-term, adaptive changes.
These processes are final-step controls that directly in-
fluence 2,3-DPG concentrations. The primary stimuli that
trigger these final steps include the following:
1. Decreased delivery of O
2
to tissues as a result of
anemia, altitude, cardiac insufficiency, or pulmonary
disease.
2. Thyroxine (which may directly stimulate
bisphosphoglycerate mutase), androgens (which act
partly by increasing erythropoiesis), and other
hormones.
3. Polycythemia, which decreases the intraerythrocytic
concentration of 2,3-DPG.
Whether the shift in the
02
-dissociation curve that
accompanies changes in the concentration of 2,3-DPG
is beneficial depends largely on the oxygen saturation
of arterial blood. The 2,3-DPG concentration can vary
widely among patients with the same disease. For ex-
ample, in severe pulmonary disease, the increase in
2,3-DPG concentration ranges from 0% to 100%; in
leukemia with depressed production of erythrocytes, el-
evations of 20-150% occur; in iron deficiency, increases
range from 40% to 75%.
2,3-DPG and, to a lesser extent, ATP concentrations de-
crease rapidly in blood that is stored even for a few days
