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Mechanistic Insights into Prostanoid Transformations Catalyzed by Cytochrome P 450 . Prostacyclin and Thromboxane Biosyntheses
| Content Provider | Semantic Scholar |
|---|---|
| Author | Yanai, Tetsuya K. Mori, Seiji |
| Copyright Year | 2011 |
| Abstract | Cytochrome P450s (P450) are an important class of proteins found in living organisms as they play a critical role in the metabolism of many endogenous and exogenous molecules. Examples of the former include the metabolites Prostacyclin (PGI2) and thromboxane A2 (TXA2), which are biosynthesized from the substrate prostaglandin H2 (PGH2) by the P450s, prostalyclin and thromboxane synthases, respectively. Both metabolites play a key role in renal, cardiovascular, and pulmonary diseases so greater mechanistic understanding of the processes leading to their formation is highly desirable. Unlike typical cytochrome P450 reactions such as monooxygenations, synthases do not require O2 or electron transfer from reductases for catalytic function. This is an area of active scientific interest in the area although there are several mechanistic proposals on the isomerization reactions of PGH2, many aspects of the reaction still remain unclear. Recent research highlights include resonance Raman spectroscopic analyses that show the resting state of the thromboxane synthase bound with a substrate analogue contains a low-spin six coordinate heme. In addition, X-ray crystallographic studies on prostacyclin synthase indicate that the catalytic pocket is small and hydrophobic in character. Also worth mention are recent quantum mechanical (QM) studies that indicates homolytic O−O bond cleavage of PGH2, is followed by one electron transfer from substrate to the heme, is essential for the generation of TXA2 and PGI2. In this chapter, we review the basic processes involved in heme and prostanoid chemistry and discuss the most recent studies in the area. The exclusive license for this PDF is limited to personal website use only. No part of this digital document may be reproduced, stored in a retrieval system or transmitted commercially in any form or by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in rendering legal, medical or any other professional services. Tetsuya K. Yanai and Seiji Mori 232 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://smori.sci.ibaraki.ac.jp/978-1-61122-467-2_ch8.pdf |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
