Oxygen Transport by Hemoglobin

Abstract

Hemoglobin (Hb) constitutes a vital link between ambient O 2 availability and aerobic metabolism by transporting oxygen (O 2 ) from the respiratory surfaces of the lungs or gills to the O 2 ‐consuming tissues. The amount of O 2 available to tissues depends on the blood‐perfusion rate, as well as the arterio‐venous difference in blood O 2 contents, which is determined by the respective loading and unloading O 2 tensions and Hb‐O 2 ‐affinity. S hort‐term adjustments in tissue oxygen delivery in response to decreased O 2 supply or increased O 2 demand (under exercise, hypoxia at high altitude, cardiovascular disease, and ischemia) are mediated by metabolically induced changes in the red cell levels of allosteric effectors such as protons (H + ), carbon dioxide (CO 2 ), organic phosphates, and chloride (Cl − ) that modulate Hb‐O 2 affinity. The long‐term , genetically coded adaptations in oxygen transport encountered in animals that permanently are subjected to low environmental O 2 tensions commonly result from changes in the molecular structure of Hb, notably amino acid exchanges that alter Hb's intrinsic O 2 affinity or its sensitivity to allosteric effectors. Structure‐function studies of animal Hbs and human Hb mutants illustrate the different strategies for adjusting Hb‐O 2 affinity and optimizing tissue oxygen supply. © 2012 American Physiological Society. Compr Physiol 2:1463‐1489, 2012.

Genetically based low oxygen affinities of felid hemoglobins: lack of biochemical adaptation to high-altitude hypoxia in the snow leopard

“…As a general rule, the tolerance to low P O2 at high altitude is associated with an increase in hemoglobin (Hb)-O 2 affinity that raises arterial O 2 saturation (Storz et al, 2010a;Weber, 2007). In most mammals, reversible changes in Hb-O 2 affinity are mediated by regulatory adjustments in the erythrocytic concentration of the organic phosphate 2,3-diphosphoglycerate (DPG) (Mairbaurl and Weber, 2012;Weber, 2007), a potent allosteric regulator of Hb-O 2 affinity (Benesch and Benesch, 1967;Bunn, 1980Bunn, , 1971. In human Hb, negatively charged DPG electrostatically binds in the symmetric cationic cleft between the paired β-subunits, including strong interactions with positively charged β82Lys and β2His and weaker interactions with the β-chain N-termini and β143His (Richard et al, 1993).…”

Phenotypic plasticity in blood-oxygen transport in highland and lowland deer mice

“…Some of these adjustments involve reversible changes in O 2 transport by red blood cells (RBCs), which is a function of the O 2 -carrying capacity of the blood (regulated by erythropoiesis) and blood-O 2 affinity [regulated by allosteric effectors of hemoglobin (Hb) function]. Mammals that are native to high-altitude environments are typically characterized by a suite of hematological and vascular traits that includes an elevated blood-O 2 affinity, a normal or slightly increased hematocrit (Hct), and increased muscle capillary density (Hall et al, 1936;Chiodi, 1962;Bullard et al, 1966;Bullard, 1972;Monge and León-Velarde, 1991;Weber, 1995;Weber, 2007;Storz et al, 2010b;Mairbäurl and Weber, 2012). In comparisons between species or conspecific populations that are native to different elevational zones, common-garden and/or reciprocal-transplant experiments are required to assess whether observed physiological differences reflect fixed, genetically based differences or environmentally induced acclimatization responses (phenotypic plasticity).…”

Tissue Hypoxia: Implications for the Respiratory Clinician

“…7 In normal humans, Hb approaches full saturation at a P O 2 of Ͼ 60 -70 mm Hg. Tighter Hb binding to oxygen (a shift to the left in the oxyhemoglobin dissociation curve) means that lower levels of P O 2 are associated with near-complete saturation of Hb, and thus, tissue unloading is more difficult.…”

“…This facilitates oxygen delivery to regions that need it most. [1][2][3]6,7 Table 1 gives regional distributions of blood flow (and thus O 2 delivery) at rest. Under exercise conditions, blood flow to skeletal muscle can increase significantly, whereas blood flow to skin and intestines may decrease.…”

“…[3][4][5] At rest, in the average tissue capillary bed, only 25% of the delivered oxygen content actually leaves the blood and enters the tissues (extraction ratio). [1][2][3]6,7 This means that for every 1,000 mL of oxygen delivered per min, 250 mL is extracted by the cells, and 750 mL remains in the blood. Thus, normal oxygen consumption is ϳ250 mL/min at rest, and mixed venous oxygen saturation is ϳ75%, which correlates with a mixed venous P O 2 of 40 mm Hg.…”