Special Focus 475In addition to CO2

Special Focus 475
In addition to CO2, Cl and BPG also bind better to deoxyhemoglobin than to
oxyhemoglobin, causing a shift in equilibrium in favor of O2 release. These various
effects are demonstrated by the shift in the oxygen saturation curves for Hb in the
presence of one or more of these substances (Figure 15.29). Note that the O2-
binding curve for Hb  BPG  CO2 fits that of whole blood very well.
2,3-Bisphosphoglycerate Is an Important Allosteric Effector
for Hemoglobin
The binding of 2,3-bisphosphoglycerate (BPG) to Hb promotes the release
of O2 (Figure 15.29). Erythrocytes (red blood cells) normally contain about 4.5
mM BPG, a concentration equivalent to that of tetrameric hemoglobin molecules.
Interestingly, this equivalence is maintained in the Hb-
BPG binding stoichiome-
try because the tetrameric Hb molecule has but one binding site for BPG. This
site is situated within the central cavity formed by the association of the four sub-
units. The strongly negative BPG molecule (Figure 15.30) is electrostatically bound
via interactions with the positively charged functional groups of each Lys 82, His
2, His 143, and the NH3
-terminal group of each -chain. These positively
charged residues are arranged to form an electrostatic pocket complementary to
the conformation and charge distribution of BPG (Figure 15.31). In effect, BPG
crosslinks the two -subunits. The ionic bonds between BPG and the two -chains
aid in stabilizing the conformation of Hb in its deoxy form, thereby favoring the
dissociation of oxygen. In oxyhemoglobin, this central cavity is too small for BPG
to fit. Or, to put it another way, the conformational changes in the Hb molecule
that accompany O2 binding perturb the BPG-binding site so that BPG can no
longer be accommodated. Thus, BPG and O2 are mutually exclusive allosteric ef-
fectors for Hb, even though their binding sites are physically distinct.
BPG Binding to Hb Has Important Physiological Significance
The importance of the BPG effect is evident in Figure 15.29. Hemoglobin stripped
of BPG is virtually saturated with O2 at a pO2 of only 20 torr, and it cannot release its
oxygen within tissues, where the pO2 is typically 40 torr. BPG shifts the oxygen satu-
ration curve of Hb to the right, making the Hb an O2 delivery system eminently
suited to the needs of the organism. BPG serves this vital function in humans, most
primates, and a number of other mammals. However, the hemoglobins of cattle,
sheep, goats, deer, and other animals have an intrinsically lower affinity for O2, and
these Hbs are relatively unaffected by BPG.
Fetal Hemoglobin Has a Higher Affinity for O2 Because
It Has a Lower Affinity for BPG
The fetus depends on its mother for an adequate supply of oxygen, but its circulatory
system is entirely independent. Gas exchange takes place across the placenta. Ideally
20
0
20 40 60
pO2, torr
100
80
60
40
Percent O2 saturation
Stripped Hb
Hb + CO2
Hb + BPG
Hb + BPG + CO2
Whole blood
FIGURE 15.29 Oxygen-binding curves of blood and of
hemoglobin in the absence and presence of CO2 and
BPG. From left to right: stripped Hb, Hb  CO2, Hb 
BPG, Hb  BPG  CO2, and whole blood.
HC OPO3
2–
C
O P
H2C OPO3
2–
O O–
O–
O–
O
C
H
H
C
H
C
O
O
O
P O
–O
–O
–
FIGURE 15.30 The structure, in ionic form, of BPG or 2,3-bisphosphoglycerate, an important allosteric effector
for hemoglobin.

Kết quả (Việt) 1:

Đặc biệt tập trung 475Ngoài việc CO2, Cl và BPG cũng liên kết tốt hơn với deoxyhemoglobin hơn đểoxyhemoglobin, gây ra một sự thay đổi trong trạng thái cân bằng trong lợi của O2 phát hành. Các khác nhauhiệu ứng được chứng minh bởi sự thay đổi trong đường cong bão hòa ôxy cho Hb trong cácsự hiện diện của một hoặc nhiều của các chất (hình 15,29). Lưu ý rằng O2 -ràng buộc đường cong cho Hb BPG CO2 phù hợp của toàn bộ máu rất tốt.2,3-Bisphosphoglycerate là một Effector Allosteric quan trọng cho HemoglobinCác ràng buộc của 2,3-bisphosphoglycerate (BPG) để Hb khuyến khích việc phát hành của O2 (hình 15,29). Hồng cầu (tế bào máu đỏ) thường chứa khoảng 4,5mM BPG, nồng độ tương đương với quỹ của phân tử tetrameric hemoglobin.Điều thú vị, tương đương này được duy trì ở Hb-BPG ràng buộc stoichiome-thử vì các phân tử Hb tetrameric có nhưng trang web một ràng buộc cho BPG. Điều nàyTrang web này tọa lạc trong Trung tâm thành phố khoang hình thành bởi sự kết hợp của bốn tiểu-đơn vị. Các phân tử BPG mạnh mẽ tiêu cực (hình 15,30) là bị ràng buộc electrostaticallythông qua tương tác với các nhóm chức năng tích cực tính của mỗi Lys 82, của mình2, 143 của mình và NH3-thiết bị đầu cuối nhóm của mỗi - chuỗi. Các tích cựctính dư lượng được sắp xếp để tạo thành một bổ sung cho túi tĩnh điệnsự phân bố conformation và phí của BPG (hình 15.31). Có hiệu lực, BPGcrosslinks hai - subunits. Các liên kết ion giữa BPG và hai - dãyaid in stabilizing the conformation of Hb in its deoxy form, thereby favoring thedissociation of oxygen. In oxyhemoglobin, this central cavity is too small for BPGto fit. Or, to put it another way, the conformational changes in the Hb moleculethat accompany O2 binding perturb the BPG-binding site so that BPG can nolonger be accommodated. Thus, BPG and O2 are mutually exclusive allosteric ef-fectors for Hb, even though their binding sites are physically distinct.BPG Binding to Hb Has Important Physiological SignificanceThe importance of the BPG effect is evident in Figure 15.29. Hemoglobin strippedof BPG is virtually saturated with O2 at a pO2 of only 20 torr, and it cannot release itsoxygen within tissues, where the pO2 is typically 40 torr. BPG shifts the oxygen satu-ration curve of Hb to the right, making the Hb an O2 delivery system eminentlysuited to the needs of the organism. BPG serves this vital function in humans, mostprimates, and a number of other mammals. However, the hemoglobins of cattle,sheep, goats, deer, and other animals have an intrinsically lower affinity for O2, andthese Hbs are relatively unaffected by BPG. Fetal Hemoglobin Has a Higher Affinity for O2 Because It Has a Lower Affinity for BPGThe fetus depends on its mother for an adequate supply of oxygen, but its circulatorysystem is entirely independent. Gas exchange takes place across the placenta. Ideally20020 40 60pO2, torr100806040Percent O2 saturationStripped HbHb + CO2Hb + BPGHb + BPG + CO2Whole bloodFIGURE 15.29 Oxygen-binding curves of blood and ofhemoglobin in the absence and presence of CO2 andBPG. From left to right: stripped Hb, Hb  CO2, Hb BPG, Hb  BPG  CO2, and whole blood.HC OPO32–CO PH2C OPO32–O O–O–O–OCHHCHCOOOP O–O–O–FIGURE 15.30 The structure, in ionic form, of BPG or 2,3-bisphosphoglycerate, an important allosteric effectorfor hemoglobin.