Models of in vitro thyroglobulin iodination

Abstract

Currently available data on the mechanisms of chemical iodination of thyroglobulin (Van Zyl and Edelhoch, 1967; Lamas et al., 1970; Rolland et al., 1972) give the numbers of tyrosyl residues MIT, DIT and T 4 in relation to the quantity of iodine added to the incubating medium. Assuming that the chemical reactions are irreversible and that the duration of the experiment is sufficiently long for the reactions to be complete the experimental curves entail the definition of a minimum number of compartments. The classic model used by De Groot et al. (1971) has been simulated. It proves to be incompatible with the experimental data. A new model is required, according to which thyroglobulin would comprise tyrosine residues capable of binding one iodine atom (MIT) and tyrosine residues capable of binding two atoms of iodine (DIT); among these molecules only a certain fraction can couple to form triiodothyronine (T 3) and tetraiodothyronine or thyroxin (T 4). Three such models compatible with these biochemical constraints, have been simulated on the computer. The values of the reaction coefficients were chosen arbitrarily due to the absence of information on chemical iodination kinetics. The models agree with the data on in vitro iodination of thyroglobulin in an acellular medium. The models are used to propose experimental protocols enabling to test different hypotheses on thyroid hormone synthesis.