The Separate Effects of H<sup>+</sup> and 2,3‐DPG on the Oxygen Equilibrium Curve of Human Blood

Samaja, Michele; Winslow, R. M.

doi:10.1111/j.1365-2141.1979.tb05870.x

Cited by 37 publications

(14 citation statements)

References 15 publications

(12 reference statements)

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“…The maximal b for a single buffer is 0.575 mM H + /mM per unit pH change (Van Slyke 1922). As pK of DPG is near 7.1 (Siggaard-Andersen 1974), and red cell pH is near 7.2 (Samaja and Winslow 1979), we assumed that b due to DPG is maximal. At altitude, the ratio DPG/Hb increases steadily.…”

Section: Hemoglobinmentioning

confidence: 99%

Acid?base balance at exercise in normoxia and in chronic hypoxia. Revisiting the "lactate paradox"

Cerretelli

Samaja

2003

European Journal of Applied Physiology

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Transitions between rest and work, in either direction, and heavy exercise loads are characterized by changes of muscle pH depending on the buffer power and capacity of the tissues and on the metabolic processes involved. Among the latter, in chronological sequence: (1). aerobic glycolysis generates sizeable amounts of lactate and H(+) by way of the recently described, extremely fast (20-100 ms) "glycogen shunt" and of the excess of glycolytic pyruvate supply; (2). hydrolysis of phosphocreatine, tightly coupled with that of ATP in the Lohmann reaction, is known to consume protons, a process undergoing reversal during recovery; (3). anaerobic glycolysis sustaining ATP production in supramaximal exercise as well as in conditions of hypoxia and ischemia, is responsible for the accumulation of large amounts of lactic acid (up to 1 mol for the whole body). The handling of metabolic acids, i.e., acid-base regulation, occurs both in blood and in tissues, mainly in muscles which are the main producers and consumers of lactic acid. The role of both blood and muscle bicarbonate and non-bicarbonate buffers as well as that of lactate/H(+) cotransport mechanisms is analyzed in relation to acid-base homeostasis in the course of exercise. A section of the review deals with the analysis of the acid-base state of humans exposed to chronic hypoxia. Particular emphasis is put on anaerobic glycolysis. In this context, the so-called lactate paradox is revisited and interpreted on the basis of the most recent findings on exercise at altitude.

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Section: Hemoglobinmentioning

confidence: 99%

Acid?base balance at exercise in normoxia and in chronic hypoxia. Revisiting the "lactate paradox"

Cerretelli

Samaja

2003

European Journal of Applied Physiology

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“…However, in humans and other mammals, the hypoxia-induced increase in red cell [DPG] continues at elevations well above the threshold at which further reductions in Hb-O 2 affinity become counterproductive due to arterial desaturation (Winslow et al, 1984;Samaja et al, 2003). Even when all Hb is fully liganded with DPG (at a DPG:Hb ratio of ≥2-3), further increases in [DPG] continue to indirectly reduce Hb-O 2 affinity because the increased erythrocytic concentration of non-diffusible anions reduces cellular pH, thereby reducing Hb-O 2 affinity via the Bohr effect (Duhm, 1971;Samaja and Winslow, 1979;Mairbäurl, 1994). Consequently, the increase in plasma pH caused by respiratory alkalosis has offsetting effects in mammalian red cells: the Bohr effect promotes an increased Hb-O 2 affinity, but this is counterbalanced by the increase in intracellular [DPG] (Winslow et al, 1984;Samaja et al, 1997).…”

Section: The Role Of Hb Isoform Switching In Hypoxia Adaptationmentioning

confidence: 99%

Hemoglobin–oxygen affinity in high-altitude vertebrates: is there evidence for an adaptive trend?

Storz

2016

Journal of Experimental Biology

112

100

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In air-breathing vertebrates at high altitude, fine-tuned adjustments in hemoglobin (Hb)-O 2 affinity provide an energetically efficient means of mitigating the effects of arterial hypoxemia. However, it is not always clear whether an increased or decreased Hb-O 2 affinity should be expected to improve tissue O 2 delivery under different degrees of hypoxia, due to the inherent trade-off between arterial O 2 loading and peripheral O 2 unloading. Theoretical results indicate that the optimal Hb-O 2 affinity varies as a non-linear function of environmental O 2 availability, and the threshold elevation at which an increased Hb-O 2 affinity becomes advantageous depends on the magnitude of diffusion limitation (the extent to which O 2 equilibration at the blood-gas interface is limited by the kinetics of O 2 exchange). This body of theory provides a framework for interpreting the possible adaptive significance of evolved changes in Hb-O 2 affinity in vertebrates that have colonized high-altitude environments. To evaluate the evidence for an empirical generalization and to test theoretical predictions, I synthesized comparative data in a phylogenetic framework to assess the strength of the relationship between Hb-O 2 affinity and native elevation in mammals and birds. Evidence for a general trend in mammals is equivocal, but there is a remarkably strong positive relationship between Hb-O 2 affinity and native elevation in birds. Evolved changes in Hb function in highaltitude birds provide one of the most compelling examples of convergent biochemical adaptation in vertebrates.

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“…This indicates that they are able to extract the O 2 well, but does not explain how it is done. One possible way that has been shown in both animal and human studies is through an increased Bohr effect (Mairbaurl et al, 1990), which may be linked to increases in [2,3-DPG] (Benesch et al, 1969;Samaja & Winslow, 1979). …”

Section: Benefits Of a Leftward Shiftmentioning

confidence: 99%

“…The binding of 2,3-DPG to Hb is dependent upon temperature (Benesch et al, 1969), pH (Garby & De Verdier, 1971;Rorth et al, 1973), PCO 2 (Bauer, 1969) and the presence of anions (Benesch et al, 1969), so the extent to which it shifts the ODC (though not the direction) is variable. 2,3-DPG concentration affects both the shape and the position of the ODC (Samaja & Winslow, 1979 (Haidas et al, 1971;Edwards & Rigas, 1967). It has been reported that high concentrations of Hb are associated with decreased O 2 affinity (Bellingham et al, 1971).…”

Section: Temperaturementioning

confidence: 99%

The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude

Balaban

Duffin

Preiss

et al. 2013

Respiratory Physiology & Neurobiology

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Some animals have adapted to hypoxia by increasing their haemoglobin affinity for oxygen, but in vitro studies have not shown any change of haemoglobin affinity for oxygen in human high altitude natives or lowlanders acutely acclimatized to high altitude. We conducted the first in vivo study of the oxyhaemoglobin dissociation curve by progressively reducing arterial PO 2 while maintaining normocapnia in lowlanders at sea level, lowlanders sojourning at 3600m for two weeks and native Andeans at the same altitude. We found that the in vivo PO 2 at which haemoglobin is half-saturated (P 50 ) is higher in lowlanders at sea level (32 mmHg) than that measured in vitro (27 mmHg) and that lowlanders and highlanders do significantly increase the in vivo affinity of their haemoglobin for oxygen with exposure to high altitude. These results indicate the value of an in vivo approach for studying the oxyhaemoglobin dissociation curve.iii

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The Separate Effects of H⁺ and 2,3‐DPG on the Oxygen Equilibrium Curve of Human Blood

Cited by 37 publications

References 15 publications

Acid?base balance at exercise in normoxia and in chronic hypoxia. Revisiting the "lactate paradox"

Acid?base balance at exercise in normoxia and in chronic hypoxia. Revisiting the "lactate paradox"

Hemoglobin–oxygen affinity in high-altitude vertebrates: is there evidence for an adaptive trend?

The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude

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The Separate Effects of H+ and 2,3‐DPG on the Oxygen Equilibrium Curve of Human Blood

Cited by 37 publications

References 15 publications

Acid?base balance at exercise in normoxia and in chronic hypoxia. Revisiting the "lactate paradox"

Acid?base balance at exercise in normoxia and in chronic hypoxia. Revisiting the "lactate paradox"

Hemoglobin–oxygen affinity in high-altitude vertebrates: is there evidence for an adaptive trend?

The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude

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The Separate Effects of H⁺ and 2,3‐DPG on the Oxygen Equilibrium Curve of Human Blood