Thyroid peroxidase activity is inhibited by amino acids

Normal in vitro thyroid peroxidase (TPO) iodide oxidation activity was comp letely inhibited by a hydrolyzed TPO preparation (0.15 mg/ml) or hydrolyzed bovine serum albumin (BSA, 0.2 mg/ml). A pancreatic hydrolysate of casein (trypticase peptone, 0.1 mg/ml) and some amino acids (cysteine, tryptophan and methionine, 50 mu M each) also inhibited the TPO iodide oxidation react ion completely, whereas casamino acids (0.1 mg/ml), and tyrosine, phenylala nine and histidine (50 mu M each) inhibited the TPO reaction by 54% or less . A pancreatic digest of gelatin (0.1 mg/ml) or any other amino acid (50 mu M) tested did not significantly decrease TPO activity. The amino acids tha t impair iodide oxidation also inhibit the TPO albumin iodination activity. The inhibitory amino acids contain side chains with either sulfur atoms (c ysteine and methionine) or aromatic rings (tyrosine, tryptophan, histidine and phenylalanine). Among the amino acids tested, only cysteine affected th e TPO guaiacol oxidation reaction, producing a transient inhibition at 25 o r 50 mu M. The iodide oxidation inhibitory activity of cysteine, methionine and tryptophan was reversed by increasing iodide concentrations from 12 to 18 mM, while no such effect was observed when the cofactor (H2O2) concentr ation was increased. The inhibitory substances might interfere with the enz yme activity by competing with its normal substrates for their binding site s, binding to the free substrates or reducing their oxidized form.