Linked Life Data

1537457

Source:http://linkedlifedata.com/resource/pubmed/id/1537457

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1992-3-30
pubmed:abstractText
The cytochrome P450 enzyme systems catalyze the metabolism of a wide variety of naturally occurring and foreign compounds by reactions requiring NADPH and O2. Cytochrome P450 also catalyzes peroxide-dependent hydroxylation of substrates in the absence of NADPH and O2. Peroxidases such as chloroperoxidase and horseradish peroxidase catalyze peroxide-dependent reactions similar to those catalyzed by cytochrome P450. The kinetic and chemical mechanisms of the NADPH and O2-supported dealkylation reactions catalyzed by P450 have been investigated and compared with those catalyzed by P450 and peroxidases when the reactions are supported by peroxides. Detailed kinetic studies demonstrated that chloroperoxidase- and horseradish peroxidase-catalyzed N-demethylations proceed by a Ping Pong Bi Bi mechanism whereas P450-catalyzed O-dealkylations proceed by sequential mechanisms. Intramolecular isotope effect studies demonstrated that N-demethylations catalyzed by P450s and peroxidases proceed by different mechanisms. Most hemeproteins investigated catalyzed these reactions via abstraction of an alpha-carbon hydrogen whereas reactions catalyzed by P-450 and chloroperoxidase proceeded via an initial one-electron oxidation followed by alpha-carbon deprotonation. 18O-Labeling studies of the metabolism of NMC also demonstrated differences between the peroxidases and P450s. Because the hemeprotein prosthetic groups of P450, chloroperoxidase, and horseradish peroxidase are identical, the differences in the catalytic mechanisms result from differences in the environments provided by the proteins for the heme active site. It is suggested that the axial heme-iron thiolate moiety in P450 and chloroperoxidase may play a critical role in determining the mechanism of N-demethylation reactions catalyzed by these proteins.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0892-6638
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
686-94
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Mechanisms of cytochrome P450 and peroxidase-catalyzed xenobiotic metabolism.
pubmed:affiliation
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review