The evolution of novel hemoglobin functions and physiological innovation

Hemoglobin ◽  
2018 ◽  
pp. 152-175
Author(s):  
Jay F. Storz
Keyword(s):  
Blood Cell ◽  
Case Studies ◽  
Red Blood Cell ◽  
Adaptive Radiation ◽  
Respiratory Function ◽  
Teleost Fishes ◽  
Root Effect ◽  
Allosteric Properties

Chapter 7 explores the evolution of novel hemoglobin functions and physiological innovations. In the epic sweep of life’s history on Earth, globin proteins such as vertebrate hemoglobin were only recently co-opted for a respiratory function in circulatory O2 transport. Even after blood-O2 transport became an entrenched feature of vertebrate physiology, red blood cell hemoglobins evolved additional specializations of function in particular lineages. In some cases, like the Root effect of fish hemoglobins, these new functions represent key physiological innovations that have contributed to adaptive radiation. This chapter explores several case studies of how the evolution of novel allosteric properties have enhanced and expanded the physiological capacities of particular vertebrate groups, with an emphasis on teleost fishes and crocodilians.

scholarly journals Molecular Modelling of Human Red Blood Cell Pyruvate Kinase: Structural Implications of a Novel G1091 to A Mutation Causing Severe Nonspherocytic Hemolytic Anemia

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4987-4995 ◽  
Author(s):  
Wouter W. van Solinge ◽  
Rob J. Kraaijenhagen ◽  
Gert Rijksen ◽  
Richard van Wijk ◽  
Bjarne B. Stoffer ◽  
...  
Keyword(s):  
Blood Cell ◽  
Pyruvate Kinase ◽  
Hemolytic Anemia ◽  
Red Blood Cell ◽  
Molecular Modelling ◽  
Human Liver ◽  
The Other ◽  
Salt Bridges ◽  
Compound Heterozygotes ◽  
Allosteric Properties

Abstract We present a novel G1091 to A mutation in the human liver and red blood cell (RBC) pyruvate kinase (PK) gene causing severe hemolytic anemia. In two families, three children were severely PK-deficient compound heterozygotes exhibiting the G1091 to A mutation and a common G1529 to A mutation on the other allele. In one family, the mother, a G1091 to A heterozygote, later had a second baby with a new husband, also a G1091 to A carrier. The baby was homozygous for the G1091 to A mutation and died 6 weeks after birth from severe hemolysis. Both mutant alleles were expressed at the RNA level. The G1091 to A mutation results in the substitution of a conserved glycine by an aspartate in domain A of RBC PK, whereas the G1529 to A mutation leads to the substitution of a conserved arginine residue with glutamine in the C-domain. Molecular modelling of human RBC PK, based on the crystal structure of cat muscle PK, shows that both mutations are located outside the catalytic site at the interface of domains A and C. The mutations are likely to disrupt the critical conformation of the interface by introducing alternative salt bridges. In this way the Gly364 to Asp and Arg510 to Gln substitutions may cause PK deficiency by influencing the allosteric properties of the enzyme.

scholarly journals Influence of Haemoglobin Conformation, Nitrite and Eicosanoids on K+ Transport Across the Carp Red Blood Cell Membrane

1992 ◽  
Vol 171 (1) ◽  
pp. 349-371 ◽  
Author(s):  
FRANK B. JENSEN
Keyword(s):  
Membrane Potential ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Quaternary Structure ◽  
Large Fraction ◽  
Nordihydroguaiaretic Acid ◽  
K Uptake ◽  
Root Effect ◽  
T State ◽  
K Transport

The regulation of K+ transport across the red blood cell (RBC) membrane by haemoglobin (Hb) conformation was studied in carp, and the K+ transport mechanisms were identified. When a large proportion of Hb in the R quaternary structure was secured by oxygenation of blood at pH8.14, a net RBC K+ efflux was induced, which was accompanied by RBC shrinkage. This K+ efflux was resistant to ouabain and inhibited by furosemide and DIDS and by substitution of NO3− for Cl−, showing it to result from a K+/Cl− cotransport mechanism. Deoxygenation of the RBCs (Hb in T structure) eliminated the Cl−-dependent K+ efflux and resulted in a net K+ uptake via the Na+/K+ pump. These changes were fully reversible. Nitrite-induced methaemoglobin formation in deoxygenated blood, which converts a large fraction of the T structure Hb into an R-like conformation, shifted the K+ uptake to a Cl−-dependent K+ efflux similar to that seen in oxygenated cells. When the allosteric equilibrium between the R and T structures of Hb was gradually shifted towards the T state by decreases in pH, the Cl−-dependent K+ efflux from oxygenated cells decreased. At pH7.52, where the Root effect caused a potent stabilisation of the T state, the K+ efflux was reversed to a net K+ uptake. A similar change was induced in methaemoglobin-containing deoxygenated blood, since low pH also favours a T-like conformation of metHb. The variable K+ fluxes could not be related to changes in membrane potential or pH but were always directly related to the experimental modulation of the relative proportions of R- and T-structure Hb. It is proposed that Hb conformation governs K+ movements via a different binding of T and R structures to integral membrane proteins, and that a large fraction of R-structure Hb triggers the Cl−dependent K+ efflux mechanism. Application of inhibitors and a substrate of prostaglandin and leukotriene synthesis did not influence the K+ efflux from oxygenated erythrocytes. However, a fraction of the K+ efflux from nitrite-treated deoxygenated cells was inhibited by nordihydroguaiaretic acid, suggesting that a slightly larger K+ efflux from these RBCs than from oxygenated RBCs was related to leukotriene production caused by nitrite entry. A much larger influx of nitrite to deoxygenated than to oxygenated RBCs was positively correlated with the distribution ratio of H+ and the membrane potential, supporting the view that nitrite primarily enters the cells via conductive transport. The physiological implications of the results are discussed.

scholarly journals Red blood cell carbonic anhydrase mediates oxygen delivery via the Root effect in red drum

2020 ◽  
Vol 223 (22) ◽  
pp. jeb232991
Author(s):  
Angelina M. Dichiera ◽  
Andrew J. Esbaugh
Keyword(s):  
Carbonic Anhydrase ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Fold Increase ◽  
Red Drum ◽  
Sciaenops Ocellatus ◽  
Scaling Exponent ◽  
Root Effect ◽  
Tightly Coupled

ABSTRACTOxygen (O2) and carbon dioxide (CO2) transport are tightly coupled in many fishes as a result of the presence of Root effect hemoglobins (Hb), whereby reduced pH reduces O2 binding even at high O2 tensions. Red blood cell carbonic anhydrase (RBC CA) activity limits the rate of intracellular acidification, yet its role in O2 delivery has been downplayed. We developed an in vitro assay to manipulate RBC CA activity while measuring Hb-O2 offloading following a physiologically relevant CO2-induced acidification. RBC CA activity in red drum (Sciaenops ocellatus) was inhibited with ethoxzolamide by 53.7±0.5%, which prompted a significant reduction in O2 offloading rate by 54.3±5.4% (P=0.0206, two-tailed paired t-test; n=7). Conversely, a 2.03-fold increase in RBC CA activity prompted a 2.14-fold increase in O2 offloading rate (P<0.001, two-tailed paired t-test; n=8). This approximately 1:1 relationship between RBC CA activity and Hb-O2 offloading rate coincided with a similar allometric scaling exponent for RBC CA activity and maximum metabolic rate. Together, our data suggest that RBC CA is rate limiting for O2 delivery in red drum.

scholarly journals Molecular Modelling of Human Red Blood Cell Pyruvate Kinase: Structural Implications of a Novel G1091 to A Mutation Causing Severe Nonspherocytic Hemolytic Anemia

Blood ◽  
1997 ◽  
Vol 90 (12) ◽  
pp. 4987-4995 ◽  
Author(s):  
Wouter W. van Solinge ◽  
Rob J. Kraaijenhagen ◽  
Gert Rijksen ◽  
Richard van Wijk ◽  
Bjarne B. Stoffer ◽  
...  
Keyword(s):  
Blood Cell ◽  
Pyruvate Kinase ◽  
Hemolytic Anemia ◽  
Red Blood Cell ◽  
Molecular Modelling ◽  
Human Liver ◽  
The Other ◽  
Salt Bridges ◽  
Compound Heterozygotes ◽  
Allosteric Properties

We present a novel G1091 to A mutation in the human liver and red blood cell (RBC) pyruvate kinase (PK) gene causing severe hemolytic anemia. In two families, three children were severely PK-deficient compound heterozygotes exhibiting the G1091 to A mutation and a common G1529 to A mutation on the other allele. In one family, the mother, a G1091 to A heterozygote, later had a second baby with a new husband, also a G1091 to A carrier. The baby was homozygous for the G1091 to A mutation and died 6 weeks after birth from severe hemolysis. Both mutant alleles were expressed at the RNA level. The G1091 to A mutation results in the substitution of a conserved glycine by an aspartate in domain A of RBC PK, whereas the G1529 to A mutation leads to the substitution of a conserved arginine residue with glutamine in the C-domain. Molecular modelling of human RBC PK, based on the crystal structure of cat muscle PK, shows that both mutations are located outside the catalytic site at the interface of domains A and C. The mutations are likely to disrupt the critical conformation of the interface by introducing alternative salt bridges. In this way the Gly364 to Asp and Arg510 to Gln substitutions may cause PK deficiency by influencing the allosteric properties of the enzyme.

Oxygen transport in invertebrates

1985 ◽  
Vol 248 (5) ◽  
pp. R505-R514 ◽  
Author(s):  
C. P. Mangum
Keyword(s):  
Gas Exchange ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Respiratory Function ◽  
Heme Proteins ◽  
Circulatory System ◽  
O2 Transport ◽  
Phylogenetic Level ◽  
Fluid Compartments ◽  
O2 Binding

The distribution of the O2 carrying proteins suggests that the original transport system was a hemoglobin similar to the alpha-chain of hemoglobin A and packaged in a nucleated red blood cell. These molecules, which occur in large open fluid compartments, function as O2 stores for regular periods of hypoxia as well as carriers between sites of gas exchange. When the closed circulatory system first arose, the red blood cell was abandoned in favor of extracellular heme proteins, and the O2 storage function became less important. Alternative O2 carriers, hemerythrins, appear in the blood at about the same phylogenetic level as the intracellular hemoglobins, and their respiratory functions appear to be similar. The presence of hemoglobins instead of hemerythrins in the vertebrates may be an evolutionary accident. Still other O2 carriers, hemocyanins, arose separately in two specialized groups that left no descendants. Their O2 binding has all the adaptive features of vertebrate hemoglobin O2 binding, with unique features also. The respiratory function of the hemocyanins is largely limited to O2 transport, which makes a far greater contribution to aerobic metabolism than the O2 carriers found in simpler systems.

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