Hemoglobin ligands

The oxygen affinity of the derivative was shown to be about half that of unmodified hemoglobin under similar conditions, but a degree of cooperativity was preserved. Kquilihrium and kinetic ligand-binding studies on this derivative have been interpreted (62) to show a perturbed R state. It is beheved that although the reaction is between the two P-chains, aP-dimers function independentiy, probably through a flexible connection. 

Of the ten trace elements known to be essential to human nutrition, seven are transition metals. For the most part, transition metals in biochemical compounds are present as complex ions, chelated by organic ligands. You will recall (Chapter 15) that hemoglobin has such a structure with Fe2+ as the central ion of the complex. The Co3+ ion... 

Thermodynamically it would be expected that a ligand may not have identical affinity for both receptor conformations. This was an assumption in early formulations of conformational selection. For example, differential affinity for protein conformations was proposed for oxygen binding to hemoglobin [17] and for choline derivatives and nicotinic receptors [18]. Furthermore, assume that these conformations exist in an equilibrium defined by an allosteric constant L (defined as [Ra]/[R-i]) and that a ligand [A] has affinity for both conformations defined by equilibrium association constants Ka and aKa, respectively, for the inactive and active states ... 

The 3D structure of the 2,3-diphosphoglycerate (DPG) complex of hemoglobin (Hb) served to derive simple aromatic dialdehydes that mimic the function of DPG as an allosteric modulator of the oxygen affinity of Hb. Some of the resulting compounds were as active and even more active than DPG, the natural ligand [1-3]. 

Each heme unit in myoglobin and hemoglobin contains one ion bound to four nitrogen donor atoms in a square planar arrangement. This leaves the metal with two axial coordination sites to bind other ligands. One of these sites is bound to a histidine side chain that holds the heme in the pocket of the protein. The other axial position is where reversible binding of molecular oxygen takes place. 

The binding and release of oxygen by hemoglobin can be represented as a ligand-exchange equilibrium at the sixth coordination site on the Fe ion. Each of the four polypeptide chains of hemoglobin contains one heme unit, so... 

Iron is, as part of several proteins, such as hemoglobin, essential for vertebrates. The element is not available as ion but mostly as the protein ligands transferrin (transport), lactoferrin (milk), and ferritin (storage), and cytochromes (electron transport) (Alexander 1994). Toxicity due to excessive iron absorption caused by genetic abnormalities exists. For the determination of serum Fe a spectrophoto-metric reference procedure exists. Urine Fe can be determined by graphite furnace (GF)-AAS, and tissue iron by GF-AAS and SS-AAS (Alexander 1994 Herber 1994a). Total Iron Binding Capacity is determined by fuUy saturated transferrin with Fe(III), but is nowadays mostly replaced by immunochemical determination of transferrin and ferritin. 

D.W. Kraus and J.B. Wittenberg, Hemoglobins of the Lucina pectinata bacteria symbiosis I. Molecular properties, kinetics, and equilibria of reactions with ligands. J. Biol. Chem. 265, 16043—16053 (1990). 

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