Myeloperoxidase-catalyzed iodination and coupling.
Myeloperoxidase (MPO), which displays considerable amino acid sequence homology with thyroid peroxidase (TPO) and lactoperoxidase (LPO), was tested for its ability to catalyze iodination of thyroglobulin and coupling of two diiodotyrosyl residues within thyroglobulin to form thyroxine. After 1 min of incubation in a system containing goiter thyroglobulin, I-, and H2O2, the pH optimum of MPO-catalyzed iodination was markedly acidic (approximately 4.0), compared to LPO (approximately 5.4) and TPO (approximately 6.6). The presence of 0.1 N Cl- or Br- shifted the pH optimum for MPO to about 5.4 but had little or no effect on TPO- or LPO-catalyzed iodination. At pH 5.4, 0.1 N Cl- and 0.1 N Br- had a marked stimulatory effect on MPO-catalyzed iodination. At pH 4.0, however, iodinating activity of MPO was almost completely inhibited by 0.1 N Cl- or Br-. Inhibition of chlorinating activity of MPO by Cl- at pH 4.0 has been previously described. When iodination of goiter thyroglobulin was performed with MPO plus the H2O2 generating system, glucose-glucose oxidase, at pH 7.0, the iodinating activity was markedly increased by 0.1 N Cl-. Under these conditions iodination and thyroxine formation were comparable to values observed with TPO. MPO and TPO were also compared for coupling activity in a system that measures coupling of diiodotyrosyl residues in thyroglobulin in the absence of iodination. MPO displayed very significant coupling activity, and, like TPO, this activity was stimulated by a low concentration of free diiodotyrosine (1 microM). The thioureylene drugs, propylthiouracil and methimazole, inhibited MPO-catalyzed iodination both reversibly and irreversibly, in a manner similar to that previously described for TPO-catalyzed iodination.
Taurog
A
A
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.
Dorris
M L
ML
D000818:Animals; D002384:Catalysis; D002417:Cattle; D006042:Goiter / Q000378:metabolism; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism*; D007454:Iodides / Q000378:metabolism*; D007700:Kinetics; D007784:Lactoperoxidase / Q000378:metabolism; D008713:Methimazole / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism*; D011441:Propylthiouracil / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013552:Swine; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000201:enzymology / Q000378:metabolism
D007454:Iodides; D012710:Serum Albumin, Bovine; D008713:Methimazole; D011441:Propylthiouracil; D013954:Thyroglobulin; D007784:Lactoperoxidase; D009195:Peroxidase; D007453:Iodide Peroxidase