Translator Disclaimer
1 October 1996 Significance of Oxygen Affinity of Fetal and Adult Human Hemoglobins
Author Affiliations +
Abstract

The oxygen equilibrium curves of human fetal and adult hemoglobins were reconstructed from the published Adair constants. The curves were then analyzed theoretically with respect to the amount of transferred oxygen, which is directly related to the saturation difference (▵S) of hemoglobin with oxygen in the artery and vein. In fetal blood, the oxygen affinity is optimized so as to provide the maximal ▵ S value in the fetus oxygen environment. In adult blood, on the other hand, the ▵ S value is far smaller than the theoretically obtained maximum, but it is most sensitive to the P50 changes around its physiological value of 27 torr. The present results imply that adult blood reserves an oxygen transport capacity for increased oxygen demands under resting conditions, and that the oxygen affinity is optimized so as to make the Bohr effect most effective to gaseous exchange.

INTRODUCTION

The oxygen equilibrium curve (OEC) of hemoglobin (Hb) can be characterized in terms of its position, which is usually expressed by the oxygen pressure at half saturation of Hb with oxygen (P50), as well as of its shape, which is quantitatively expressed by the highest slope of the Hill plot (nmax). The position of OEC is shifted on changes in the pH or the concentration of organic phosphates in red blood cells.

In our previous paper (Kobayashi et al., 1994a), we have reported on the significance of the slope of OEC in the oxygen transport efficiency of Hb. The efficiency was expressed by the quantity S' (=dS/dP), where S and P denote the oxygen saturation and the partial pressure of oxygen, respectively, and the plot of S' against P yielded a bell-shaped curve. The ordinate and abscissa readings of the maximum point in the curve give the maximal oxygen transport efficiency, S'max, and the corresponding partial pressure of oxygen, Pdmax, respectively. The Pdmaxvalue for human fetal whole blood was found to be 17 torr under physiological conditions and it corresponds to the steepest part of the OEC. It seems that fetal blood is best adapted to its physiological conditions with the partial pressure of oxygen between 35 and 15 torr and consequently not well to severe hypoxic conditions. On the other hands, the Pdmax value of 22 torr found for the whole blood of human adult under resting physiological conditions (giving S=0.38), was definitely lower than the oxygen pressure in the mixed venous blood (40 torr). It was therefore concluded that a considerable portion of the oxygen transport capacity of adult blood is reserved for large oxygen demand that may occur under severe exercise conditions.

In this paper, the difference in arterio-venous oxygen saturation, ▵S, and its differential value of d▵ S/dP50 were calculated as new indices for oxygen transport function, and a theoretical examination was made on the significance of the P50 values of fetal and adult blood.

MATERIALS AND METHODS

The experimental data used for the present analysis were of 40 OEC data sets previously published for human adult and fetal hemoglobins (Imai, 1982; Imai and Yonetani, 1975; Imaizumi et al., 1982; Tyuma et al., 1973). Human adult Hb consists of the two α-subunits and two βsubunits, whereas fetal Hb consists of two αsubunits and two γsubunits. Fetal Hb shows an oxygen affinity considerably higher than that of adult Hb, and thus oxygen is transferred to fetal blood effectively through the placenta. In this paper, the OECs were also reconstructed using the published values of Adair constants. According to Adair (Adair, 1926), the oxygen saturation (S) of tetrameric Hb is expressed as a function of oxygen pressure (P) as follows:

i0289-0003-13-5-661-e1.gif
where Ki (i=1 to 4) is the intrinsic constant (Adair constant) at i th oxygenation step.

All computations were carried out on a personal computer model PC-9821 Ap2 (Nippon Electric Co., Tokyo) using MS-FORTRAN.

RESULTS

Calculation of ▵S and comparison of the shape of OEC between fetal and adult Hb

The Adair constants of Hbs have been determined with reasonable accuracy from precise oxygen equilibrium data (Imai, 1982; Imai and Yonetani, 1975; Imaizumi et al., 1982; Tyuma et al., 1973), which makes it possible to analyze the OECs quantitatively. First, we defined ▵S as difference in the S values of the artery and vein, For adult blood, we used the literature values of 100 and 40 torr as the arterial and venous P, respectively (Altman and Ditter, 1975). The arterio-venous difference in S was designated as ▵S(100-40). For fetal blood, the corresponding literature values were 35 and 15 torr, respectively (Breathnach, 1991). The difference in S for fetal blood was designated as ▵S(35-15). Figure 1 shows an example of the calculation of the ▵S value. The hypothetical OECs with different P50 values were constructed from the reported Adair constants (ki, i=1 to 4) which were changed by common factors, i.e. ki→ki·constant (i=1 to 4).By doing this, the position of OEC was shifted freely without change in its shape. Unfortunately, only a few accurate OEC data sets are available for fetal Hb (Tyuma et al., 1973). In Fig. 2, the product of S'.P50(=dS/d(P/P50))was plotted against P/P50· The P and S' values were normalized by dividing by P50 to eliminate the effect of P50 difference on the shape of OEC (Kobayashi et al., 1994b). Figure 2 shows a close similarity in the shape of OEC between fetal Hb (A) and adult Hb (B), This accords with the earlier finding of Allen et al. (1953) that there is no significant difference in the shape of OEC between fetal and adult Hb.

Fig. 1.

Example of ▵S calculation. ▵S(100-40) is for adult blood and ▵S(35-15) is for fetal blood. OEC data set used for the calculation were taken from Imai (1982).

i0289-0003-13-5-661-f1.gif

Fig. 2.

S vs. P/P50 (dashed lines) and S'· P50 vs. P/P50 (solid lines) plots for human fetal (A) and adult (B) Hb. OEC data sets used for calculation were taken from Tyuma et al. (1973), and from Imai and Yonetani (1975).

i0289-0003-13-5-661-f2.gif

S vs. P50 plot for oxygen environment of fetal and adult blood

Figure 3A shows the dependence of ▵S(35-15) on P50 calculated for hypothetical OECs with nmax=3.2 for fetal blood. The value of ▵S(35-15) reached a maximum (▵S(35-15)max) at P50 = 22 torr. The theoretically obtained optimum P50 value was very close to the actual P50 value (20 torr) for the fetal blood under physiological conditions.

Fig. 3.

(A) The effect of P50 on saturation difference, ▵S(35-15), in physiological oxygen environment of fetal blood. (B) The effect of P50 on arterio-venous saturation difference, ▵S(100-40), in physiological oxygen environment of adult blood, (open arrow) theoretically obtained optimum P50 and (closed arrow) physiological P50. OEC data set used for the calculation were taken from Imai (1982).

i0289-0003-13-5-661-f3.gif

Figure 3B shows the amount of oxygen released in adult vein (▵S) as a function of P50· The P values in artery and vein were assumed to be 100 and 40 torr, respectively. The ▵S(100-40) reached a maximum (▵S(100-40)max) value of 0.52 at P50=62 torr. This was much higher than the ▵S(100-40) value of 0.23 calculated at P50=27 torr for adult blood under the physiological conditions.

S' vs. P plot for oxygen environment of fetal and adult blood

Figure 4A shows an S' vs. P plot calculated for the OEC of fetal (P50=20 torr) blood under the physiological conditions. The OEC changes steeply in the fetal oxygen environment (35-15 torr), and the maximum point for S'was found within the physiological Prange. This implies that fetal blood provides constantly a maximum oxygen-transport efficiency and has almost no reserve for increased oxygen demands.

Fig. 4.

S' vs. P plots for fetal (A) and adult (B) blood. Solid lines indicate S and S'under physiological oxygen environment of fetal (35-15 torr) and adult (100-40 torr) blood. The OEC data set used for the calculation are the same as in Fig. 3.

i0289-0003-13-5-661-f4.gif

By using the classical Hill equation, Willford et al. (1982) theoretically examined the optimal position of fetal Hb OEC at which the maximum amount of oxygen can be released from Hb. They showed that the optimal P50 can be expressed as the square root of the product of arterial and venous P values. The calculated P50 value for the present case was 23 torr, this being slightly greater but very close to the optimum P50 value (22 torr) noted above.

On the other hand, the S' vs. P plot for OEC (P50=27 torr) of adult blood under physiological conditions is shown in Fig. 4B. As seen in the figure, the S' value at adult venous P (40 torr) is low, this implying that under resting conditions the advantage of cooperativity is scarcely utilized. However, under hard exercise conditions, P will probably decrease to near 20 torr, which is almost equal to the Pdmaxvalue (22 torr) of OEC with P50 = 27 torr. Figure 4B also indicates that, in adults, the gradual increase in the S' value occurs at P below 40 torr, and adult blood is regarded as holding a reserve to meet the increase in the oxygen demand during severe exercise.

Another significance of adult blood P50

In the physiological oxygen environment for adult blood, the maximum value of ▵S is obtained at P50 =62 torr (Fig. 3B). However, a blood with this P50 value cannot fill an increased oxygen demands any more. To find the significance of the P50 of the adult blood, we have calculated the first derivatives of ▵S(100-40) with respect to P50 (d▵S(100-40)/dP50) as a function of P50(Fig. 5A), and found that the value of d▵ s(100-40)/dP50 reached a maximum at P50=29 torr. This implies that ▵S(100-40) is most sensitive to P50 change at P50 =29 torr. It should be noted that the theoretically obtained optimum P50 value (29 torr) is nearly equal to the experimental P50 (27 torr) of the adult blood under the physiological conditions. To ascertain the results, the same calculation was carried out for the 38 OEC data sets of human adult Hb (Imai, 1982; Imai and Yonetani, 1975; Imaizumi et al., 1982; Tyuma et al., 1973) giving different values of nmax. It was found that the P50 values which give the maximum d▵S(100-40)/dP50fell in a narrow range from 27 to 31 torr (Fig. 6).

Fig. 5.

The first derivative for the arterio-venous saturation difference, d▵S/dP50, for adult (A) and fetal (B) blood plotted against P50· (open arrow) theoretically obtained optimum P50 and (closed arrow) physiological P50· The OEC data set used for the calculation are the same as in Fig. 3.

i0289-0003-13-5-661-f5.gif

Fig. 6.

The plot of P50 values that maximizes d▵S(100-40)/dP50 against the nmax values. The OEC data sets used for the calculation were taken from Imai (1982), Imai and Yonetani (1975), Imaizumi et al. (1982) and Tyuma et al. (1973).

i0289-0003-13-5-661-f6.gif

The change in the position of OEC, which actually occurs in the physiological conditions, is known as the Bohr effect. Metabolically produced C02 acidifies the blood in the tissue capillaries, causing a rightward shift of the OEC that in turn promotes oxygen release (see the broken line of Fig. 5A). The magnitude of the Bohr shift is expressed by the Bohr coefficient (▵logP50/▵pH). Our present analysis shown in Fig. 5A indicates that the human adult blood with P50=27 torr is designed to make the Bohr shift most efficient at the arterial P of 100 torr and the venous P of 40 torr.

In the oxygen environment of fetal blood, the value of d▵S(35-15)/dP50 reaches a maximum when P50 is 13 torr (Fig. 5B). At P50 of 20 torr, the value of d▵S(35-15)/dP50 is far below the maximum, though its value is still not very small compared with the adult one. It should be pointed out that, in the fetal blood, the Bohr effect still plays an important role in C02 transport by generating a large arterio-venous difference in C02 content.

In conclusion, the fetal blood is designed to optimize the P50 so that ▵S(35-15) is maximized, whereas the adult blood is designed so as to keep a reserve for oxygen demands at exercise and to make the Bohr effect most effective under resting conditions.

REFERENCES

  1. G. S. Adair 1926. The oxygen dissociation curve of hemoglobin. J Biol Chem 63:529–545. Google Scholar
  2. D. W. Allen, J. Wyman, and C. A. Smith . 1953. The oxygen equilibrium of fetal and adult human hemoglobin. J Biol Chem 203:81–87. Google Scholar
  3. P. L. Altman and D. S. Ditter . 1975. Respiration and Circulation. Federation of American Societies for Experimental Biology. Bethesda. Google Scholar
  4. C. S. Breathnach 1991. The stability of the fetal oxygen environment. Irish J Medical Science 160:189–191. Google Scholar
  5. K. Imai 1982. Allosteric Effects in Haemoglobin. Cambridge University Press. London and New York. Google Scholar
  6. K. Imai and T. Yonetani . 1975. pH dependence of the Adair constants of human hemoglobin. J Biol Chem 250:2227–2231. Google Scholar
  7. K. Imaizumi, K. Imai, and I. Tyuma . 1982. Linkage between carbon dioxide binding and four-step oxygen binding to hemoglobin. J Mol Biol 159:703–719. Google Scholar
  8. M. Kobayashi, K. Ishigaki, M. Kobayashi, and K. Imai . 1994a. Shape of the haemoglobin-oxygen equilibrium curve and oxygen transport efficiency. Respir Physiol 95:321–328. Google Scholar
  9. M. Kobayashi, G. Satho, and K. Ishigaki . 1994b. Sigmoid shape of the oxygen equilibrium curve and the P50of human hemoglobin. Experientia 50:705–707. Google Scholar
  10. I. Tyuma, K. Imai, and K. Shimizu . 1973. Analysis of oxygen equilibrium of hemoglobin and control mechanism of organic phosphates. Biochemistry 12:1491–1498. Google Scholar
  11. D. C. Willford, E. P. Hill, and W. Y. Moores . 1982. Theoretical analysis of optimal P50. J Appl Physiol 52:1043–1048. Google Scholar
Michiyori Kobayashi, Shoko Kimura, Ken-Ichi Ishigaki, Nobuo Makino and Kiyohiro Imai "Significance of Oxygen Affinity of Fetal and Adult Human Hemoglobins," Zoological Science 13(5), (1 October 1996). https://doi.org/10.2108/zsj.13.661
Received: 8 May 1996; Accepted: 1 June 1996; Published: 1 October 1996
JOURNAL ARTICLE
4 PAGES


SHARE
ARTICLE IMPACT
Back to Top