Oxygen Transport in Red Blood Cells

Proceedings of the 12th Aharon Katzir Katchalsky Conference, Tours, France, 4–7 April 1984

Claude Nicolau

• Publisher: Pergamon
• Year: 2013
• Print ISBN: 9780080308005
• eBook ISBN: 9781483160443
• Topic: Medicine
• Subtopic: Physiology

Oxygen Transport in Red Blood Cells contains the proceedings of the 12th Aharon Katzir Katchalsky Conference held at Tours, France on April 4-7, 1984. Organized into 16 chapters, this book begins with a discussion on the influence of heme pocket geometry on ligand binding to heme proteins. Subsequent chapters describe a genetic approach to producing oxygen affinity differences; clinical importance of the oxygen transport function of preserved red blood cells; methods for the measurement of oxygen equilibrium curves of red cell suspensions and hemoglobin solutions; and aspects of oxygen supply to tissue. Other chapters elucidate interactions between hemoglobin and erythrocyte membrane and membrane protein oxidation; incorporation of allosteric effectors of hemoglobin in red blood cells; and significance of low hemoglobin oxygen affinity.The interaction of ligands and other molecules with hemoglobin and the storage of red blood cells having incorporated exogenous allosteric effectors of hemoglobin are also explained.

Influence of Heme Pocket Geometry on Ligand Binding to Heme Proteins

K.H. Winterhalter and E.E. Di Iorio, Laboratorium fuer Biochemie I, Eidgenoessische Technische, Hochschule, ETH-Zentrum, Universitaetsstrasse 16, 8092 Zurich, Switzerland

Publisher Summary

This chapter discusses the influence of heme pocket geometry on ligand binding to heme proteins. For the binding to the heme-iron of a ligand molecule, three steps characterized by energy barriers are distinguished: (1) penetration of the ligand from the solvent, across the structured hydration shell, into the protein matrix; (2) diffusion through the matrix into the heme pocket; and (3) the binding to iron from inside the pocket. The geometry of the heme pocket is influenced by two main factors. The most prominent one is genetic variety of the protein. For a given heme protein, the geometry is influenced by fluctuations of the proteic structure and steric changes in the prostetic group and are caused by alterations of the position of the iron relative to the heme plane. This is often caused by structural changes in the protein and frequently entails changes of the position of the heme within the pocket.

Oxygen binding, and its delivery to the place of consumption, is the continent in which the city of oxygen transport by red blood cells lies. The problem of oxygen transport is old, but new insight is gained every year. Table I gives an overview of the continent and the roads to and from the city. The levels of traffic regulation, as they are conceived presently, are also given.

Table I

The levels of regulation of O₂ supply to tissues

Compartment	Level	Some parameters
A External	1. pO2	Altitude
	2. Aeration of alveolae	State of Lung
	3. Permeability of alveolae	State of Lung
B Blood	1. O2 capacity	Erythropoietin levels
	2. O2 uptake by RBC	Potency of circulation, membrane permeability, diffusion in cytoplasm, others?
	3. O2 affinity of hemoglobin	Genetic material, allosteric effectors, CO2, pH, others?
	4. O2 dissociation in the periphery	As for B2 and B3; O2 gradient
C Intracellular in tissues	1. Myoglobin	State of exercise, hormonal regulation
	2. Uptake into organelles (Mitochondria, microsomes, peroxysomes, plasmamembranes	Diffusion, others?

Oxygen, at its various places of consumption, is needed for a variety of different types of metabolism. They are summarized in table II. From this table it is evident that oxygen affects all walks of biochemistry in areobic organisms, from energy production to cancer.

Table II

Types of metabolisms in which oxygen is paramount

Type	Main organelle	Examples
Energy metabolism	Mitochondria Chloroplasts	Respiratory chain; photosystem 1 and 2
Katabolic	Peroxysomes	Conversion of octanoate to H2O2; D-amino acid breakdown; urate and L-alphahydroxy-acids metabolism
Modification of metabolites	Microsomes	Synthesis of carcinogens and tumor promotors by terminal oxygenase systems; prostaglandin and adrenalin synthesis
Biosynthesis and Katabolism	Cytoplasm	Some steps of aminoacid katabolism, e.g. tryptophane pyrrolase
Bacterial killing	Plasmamembrane of white cells; natural killer cells	Polymorphonuclear leucocyte superoxide synthetase

As many of the regulatory mechanisms of oxygen transport by red blood cells (Table I.B) will be discussed by other participants of this conference, the topic of this talk is limited to the innermost events inside the hemoglobin molecule.

The overall anatomy of a sperm whale myoglobin (SW-Mb) molecule (also representative of a hemoglobin chain) is given in fig. 1. For the binding to the heme-iron of a ligand molecule, coming from the solvent, at least three steps, characterized by energy barriers (Austin et. al., 1975), must be distinguished:

Figure 1 Cross section of a sperm whale myoglobin molecule

1. Penetration of the ligand from the solvent, across the structured hydration shell, into the protein matrix.

2. Diffusion through the matrix into the heme pocket.

3. Binding to iron from inside the pocket.

The corresponding reaction scheme is su...

Table of contents

• Cover image
• Title page
• Table of Contents
• ADVANCES IN THE BIOSCIENCES
• Copyright
• Foreword
• ERRATUM
• List of Contributors
• Chapter 1: Influence of Heme Pocket Geometry on Ligand Binding to Heme Proteins
• Chapter 2: A Genetic Approach to Producing Oxygen Affinity Differences
• Chapter 3: Oxygen-Bioenergetics and 31P NMR in vivo
• Chapter 4: Clinical Importance of the Oxygen Transport Function of Preserved Red Blood Cells
• Chapter 5: Methods for the Measurement of Oxygen Equilibrium Curves of Red Cell Suspensions and Hemoglobin Solutions
• Chapter 6: Aspects of Oxygen Supply to Tissue
• Chapter 7: Interactions between Hemoglobin and Erythrocyte Membrane and Membrane Protein Oxidation
• Chapter 8: Interactions between O2 and CO2 in Blood
• Chapter 9: Oxygen Supply to the Brain
• Chapter 10: Oxygen Supply to the Brain Under Hypoxic and Hyperoxic Conditions
• Chapter 11: Nuclear Medicine Investigations of the Oxygen Dependent Metabolism of the Heart Muscle
• Chapter 12: Incorporation of Allosteric Effectors of Hemoglobin in Red Blood Cells. Biochemical and Physiological Effects
• Chapter 13: Flow Compensation with Oxygen Equilibrium Curve Shifts
• Chapter 14: Significance of Low Hemoglobin Oxygen Affinity
• Chapter 15: Hemoglobin Solutions as Oxygen Carriers: Ligands and Other Molecules Interactions with Hemoglobin
• Chapter 16: Storage of Red Blood Cells having Incorporated Exogenous Allosteric Effectors of Hemoglobin
• Index