HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guengerich, F. P. Search for Related Content PubMed PubMed Citation Articles by Guengerich, F. P. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 262, Issue 18, 8459-8462, 06, 1987

Oxidative cleavage of carboxylic esters by cytochrome P-450

FP Guengerich

Cytochrome P-450 was demonstrated to catalyze the oxidative cleavage of carboxylic acid esters to the corresponding carboxylic acids. 2,6- Dimethyl-4-phenyl-3,5-pyridinedicarboxylic acid diethyl ester and related dialkyl esters were shown to serve as substrates in NADPH- fortified rat liver microsomes and reconstituted systems containing purified cytochrome P-450 enzymes. The ethyl group gave rise to acetaldehyde. The reactions proceed with large kinetic deuterium isotope effects, consistent with the view that P-450 abstracts a hydrogen atom in the mechanism. Oxygen rebound to the radical site is then postulated to complete the reaction and lead to a hemiacetal-like structure which collapses to give the products. Rate studies with differing alkyl substituents showed that the reaction was more rapid with removal of an ethyl than a methyl or isopropyl group, consistent with the view that the ethyl optimizes steric and inductive effects. Oxidative cleavage of carboxylic acid esters has little biochemical precedent, due to the difficult character of the reaction, and should be considered as an alternative to direct hydrolysis.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. L. Polsky-Fisher, H. Cao, P. Lu, and C. R. Gibson EFFECT OF CYTOCHROMES P450 CHEMICAL INHIBITORS AND MONOCLONAL ANTIBODIES ON HUMAN LIVER MICROSOMAL ESTERASE ACTIVITY Drug Metab. Dispos., August 1, 2006; 34(8): 1361 - 1366. [Abstract] [Full Text] [PDF]

				U. Hoffler and B. I. Ghanayem INCREASED BIOACCUMULATION OF URETHANE IN CYP2E1-/- VERSUS CYP2E1+/+ MICE Drug Metab. Dispos., August 1, 2005; 33(8): 1144 - 1150. [Abstract] [Full Text] [PDF]

				B. Clement and K. Lopian Characterization of in Vitro Biotransformation of New, Orally Active, Direct Thrombin Inhibitor Ximelagatran, an Amidoxime and Ester Prodrug Drug Metab. Dispos., May 1, 2003; 31(5): 645 - 651. [Abstract] [Full Text] [PDF]

				F. P. Guengerich, G. P. Miller, I. H. Hanna, H. Sato, and M. V. Martin Oxidation of Methoxyphenethylamines by Cytochrome P450 2D6. ANALYSIS OF RATE-LIMITING STEPS J. Biol. Chem., September 6, 2002; 277(37): 33711 - 33719. [Abstract] [Full Text] [PDF]

				Z. Zeng and N. W. Andrew Characterization of Eprinomectin N-Deacetylase in Rats Drug Metab. Dispos., February 1, 1999; 27(2): 269 - 273. [Abstract] [Full Text]

				S. Kudo, H. Okumura, G. Miyamoto, and T. Ishizaki Cytochrome P-450 Isoforms Involved in Carboxylic Acid Ester Cleavage of Hantzsch Pyridine Ester of Pranidipine Drug Metab. Dispos., February 1, 1999; 27(2): 303 - 308. [Abstract] [Full Text]

				F. P. Guengerich, C.-H. Yun, and T. L. Macdonald Evidence for a 1-Electron Oxidation Mechanism in N-Dealkylation of N,N-Dialkylanilines by Cytochrome P450 2B1. KINETIC HYDROGEN ISOTOPE EFFECTS, LINEAR FREE ENERGY RELATIONSHIPS, COMPARISONS WITH HORSERADISH PEROXIDASE, AND STUDIES WITH OXYGEN SURROGATES J. Biol. Chem., November 1, 1996; 271(44): 27321 - 27329. [Abstract] [Full Text] [PDF]