Interactions of Porphyrins With Proteins

Abstract

While attention is focused in the present symposium on diagnosis and therapy of porphyrias, the possible role played by some proteins in the relevant physiologic processes is also considered. In some cases, the binding parameters of various tetrapyrroles to proteins found in the serum or in liver cytosol have been estimated but only few reliable binding constants have been determined (e.g., 1–5 and references cited). Under in vivo conditions the binding characteristics may be different, since not only factors such as the pH, temperature, etc., may affect the binding, but also various other protein ligands present under physiologic conditions. However, equilibrium constants (K) are a measure of thermodynamic affinities and, hence, of standard free energy differences only. For a simple binding process, ^Kass ^{= k}o n/^koff. Therefore, the determination of the rate constants ^kon and ^koff for association and dissociation of a ligand is required for a more complete and realistic appraisal of the processes involved in the transport of porphyrins and other tetrapyrroles by proteins. However, such data are even more scanty than equilibrium constants, partly due to experimental difficulties. According to our preliminary measurements, ^koff is of the order of 10^-3 sec^-1 at 2 5°C and pH 7.4 for the dissocia tion of ferriheme from human serum albumin, as determined by transfer experiments to apomyoglobin under certain conditions.