HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Ether link cleavage is the major pathway of iodothyronine metabolism in the phagocytosing human leukocyte and also occurs in vivo in the rat.

Abstract
These studies were performed to test the hypothesis that ether link cleavage (ELC) is an important pathway for the metabolism of thyroxine (T(4)) in the phagocytosing human leukocyte. When tyrosyl ring-labeled [(125)I]T(4)([Tyr(125)I]T(4)) was incubated with phagocytosing leukocytes, 50% of the degraded label was converted into [(125)I]3,5-diiodotyrosine ([(125)I]DIT). Of the remaining [Tyr(125)I]T(4) that was degraded, two-thirds was recovered as [(125)I]-nonextractable iodine ([(125)I]NEI), and one-third as [(125)I]iodide. The production of [(125)I]DIT was not observed when phenolic ring-labeled [(125)I]T(4) ([Phen(125)I]T(4)) was used, although [(125)I]NEI and [(125)I]iodide were produced. None of these iodinated compounds were formed in leukocytes that were not carrying out phagocytosis. The fraction of T(4) degraded by ELC was decreased by the addition of unlabeled T(4) and by preheating the leukocytes, findings which suggested that the process was enzymic in nature. ELC was enhanced by the catalase inhibitor aminotriazole, and was inhibited by the peroxidase inhibitor propylthiouracil, suggesting that the enzyme is a peroxidase and that hydrogen peroxide (H(2)O(2)) is a necessary cofactor in the reaction. To test this hypothesis, studies were performed in several inherited leukocytic disorders. ELC was not observed in the leukocytes of patients with chronic granulomatous disease, in which the respiratory burst that accompanies phagocytosis is absent. ELC was normal in the leukocytes of two subjects homozygous for Swiss-type acatalasemia, and aminotriazole enhanced ELC in these cells to an extent not significantly different from that observed in normal cells. ELC was normal in the leukocytes of a patient with myeloperoxidase deficiency, but could be induced by the incubation of [Tyr(125)I]T(4) with H(2)O(2) and horseradish peroxidase in the absence of leukocytes. The in vivo occurrence of ELC in the rat was confirmed by demonstrating the appearance of [(125)I]DIT in serum from parenterally injected [(125)I]3,5-diiodothyronine, but no [(125)I]DIT was produced when [(125)I]3',5'-diiodothyronine was administered. FROM THESE FINDINGS WE CONCLUDE THE FOLLOWING: (a) ELC is the major pathway for the degradation of T(4) during leukocyte phagocytosis, and accounts for 50% of the disposal of this iodothyronine; (b) the NEI and iodide formed by phagocytosing cells are derived from the degradation of the phenolic and tyrosyl rings of T(4), although ELC per se accounts for only a small fraction of these iodinated products; (c) the process by which ELC occurs is enzymic in nature, and its occurrence requires the presence of the respiratory burst that accompanies phagocytosis; (d) the enzyme responsible for ELC is likely to be a peroxidase, although a clear role for myeloperoxidase as the candidate enzyme remains to be established; (e) iodothyronines are also degraded by ELC in vivo, and the quantitative importance of this pathway in various pathophysiological states requires further investigation.
AuthorsA G Burger, D Engler, U Buergi, M Weissel, G Steiger, S H Ingbar, R E Rosin, B M Babior
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 71 Issue 4 Pg. 935-49 (Apr 1983) ISSN: 0021-9738 [Print] United States
PMID6833495 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Ethers
  • Diiodotyrosine
  • Propylthiouracil
  • Hydrogen Peroxide
  • Horseradish Peroxidase
  • Catalase
  • Thyroxine
  • Amitrole
Topics
  • Amitrole (pharmacology)
  • Animals
  • Catalase (blood)
  • Chromatography, Gel
  • Chromatography, Ion Exchange
  • Diiodotyrosine (metabolism)
  • Ethers (metabolism)
  • Granulomatous Disease, Chronic (metabolism)
  • Horseradish Peroxidase (pharmacology)
  • Humans
  • Hydrogen Peroxide (pharmacology)
  • Male
  • Metabolism, Inborn Errors (metabolism)
  • Phagocytes (analysis, metabolism)
  • Phagocytosis
  • Propylthiouracil (pharmacology)
  • Rats
  • Thyroxine (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: