CHEMISTRY, GENETICS, AND FUNCTION OF INVERTEBRATE RESPIRATORY PIGMENTS—CONFIGURATIONAL CHANGES AND ALLOSTERIC EFFECTS

Abstract

1The complex distribution and function of the invertebrate respiratory pigments is briefly reviewed.2On the basis of what is known concerning the structure of the proteins and the “active site”, it is suggested that hemoglobin-chlorocruorin, hemocyanin, and hemerythrin have originated independently. In addition, both hemoglobin and hemocyanin may be of polyphyletic origin, though the evidence for all of this is weak.3There are formidable difficulties in determination of the oxidation states or sites of attachment of the metals in hemocyanin and hemerythrin. However, oxygenation of these pigments is basically similar to that for hemoglobin, in contrast to current belief.4There is a large body of evidence suggestive that combination of a respiratory pigment with oxygen or another ligand is accompanied by changes in the secondary and tertiary structure, and sometimes in the quaternary structure as well. However, much of this evidence is more equivocal than has been realized. It has been especially difficult to sort out changes in the associated solvent from changes in the protein moiety, though it is clear that the properties of the oxygen equilibrium are fundamentally dependent on the protein structure rather than the “water lattice”.5Chemical modification studies have been especially useful in the study of such configurational changes. Applications to various invertebrate respiratory pigments of the techniques that have been heretofore used on mammalian hemoglobin has provided further evidence that the basic aspects of the oxygen equilibria are the same in spite of the polyphyletic origin of these respiratory proteins.6Evolution of the various respiratory pigments has shown repeatedly the development of complex allosteric effects. These involve homointeractions—e.g. the heme-heme interactions and the equivalent phenomena in non-heme respiratory pigments—and heterointeractions—e.g. the Bohr effect. Both of these phenomena can be either facilitating—the usual positive heme-heme interactions and the “reverse” Bohr effect—or hindering—the rare negative heme-heme interactions and the “normal” Bohr effect, or both. In addition, the interactions are frequently dependent on pH, various ions, especially calcium, quaternary structure, and intracellular modification. Thus, the Bohr effect and the heme-heme interactions are fundamentally similar allosteric phenomena, being both mediated through configurational changes.7Configurational changes and allosteric effects have appeared in enzymes, in antibody-antigen reactions, and in other aspects of protein chemistry. In addition, configurational changes may be basic to more complicated expressions of cellular function, such as nerve conduction, muscle contraction, and active transport. 8. The respiratory pigments form a most useful system for comparison with and examination of allosteric effects involved in the regulation of cellular activity. Certain general principles of regulation and amplification through negative and positive feedback systems involving allosteric effects are discussed.