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Prostacyclin and Thromboxane Synthase: New Aspects of Hemethiolate Catalysis
Author(s) -
Ullrich Volker,
Brugger Roland
Publication year - 1994
Publication title -
angewandte chemie international edition in english
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 0570-0833
DOI - 10.1002/anie.199419111
Subject(s) - thromboxane a synthase , prostacyclin , chemistry , enzyme , prostaglandin h2 , thromboxane , stereochemistry , arachidonic acid , atp synthase , thromboxanes , prostaglandin , thromboxane receptor , biochemistry , thromboxane a2 , platelet , biology , receptor , immunology
The arachidonic acid metabolites thromboxane A 2 and prostacyclin are highly potent regulators of cell physiology. They are both formed by enzymatic rearrangement of the 9,11‐epidioxy prostaglandin H 2 catalyzed, however, by thromboxane and prostacyclin synthase, respectively. The two enzymes have been isolated, sequenced, and characterized as hemethiolate (“P450”) enzymes. The different isomerization products can be explained on the same catalytic principle by a different ligation of the heme centers with the two epidioxy oxygens atoms. This requires different conformations for substrate binding at the active site, which is substantiated by the different inhibitors and amino acid sequences of the enzymes. In a hypothesis which has mechanistic principles in common with the P450‐monooxygenases and the allene oxide synthases, oxy radicals are formed first and rearrange to carbon radicals. These could then rapidly be converted into carbocations by the ferrylthiolate or iron( III )thiyl structures formed as intermediates.