Stimulation and inhibition of thyroid iodinating enzyme systems

Abstract

1. 1. A study has been made of the action of chemical agents on iodination mediated by a particulate and by a soluble calf thyroid enzyme system. The particulate enzyme has a pH optimum near 9.8 and displays only a fraction of its maximal activity at pH 7.4. 2. 2. Reduced pyridine nucleotides, tetrahydrofolic acid, and, in certain concentrations, compounds functioning in other circumstances as chelating agents (penicillamine), reducing agents (dihydroxyfumarate), sulfhydryl reagents ( N-ethylmaleimide), and disulfide reagents (cysteine) stimulate particulate iodination. These compounds may be oxidized by atmospheric O 2 with generation of H 2O 2. 3. 3. Sulfhydryl inhibitors depress particulate iodination, perhaps by interfering with H 2O 2 generation. 4. 4. Inhibition of mitochondrial electron transport does not affect iodination by the soluble enzyme system. 5. 5. Tetrahydrofolic acid, penicillamine, dihydroxyfumarate and cysteine inhibit soluble enzyme iodination. 6. 6. In the ‘soluble’ system H 2O 2 is provided, and the compounds may serve as competitive reducing agents or reduce labile reactive sites on the enzyme. 7. 7. Reduction of the soluble enzyme appears to cause irreversible damage, for efforts to reoxidize or otherwise reactivate the sulfite inhibited enzyme are unsuccessful.