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P450 cytochromes

Metabolism is still a barrier to be overcome. Some QSAR, pharmacophore, protein, and rule-based models are available to predict substrates and inhibitors of a specific cytochrome P450 isoenzyme [47-55]. [Pg.608]

An important enzyme in bio logical electron transport called cytochrome P450 gets Its name from its UV absorp tion The P stands for pig ment because it is colored and the 450 corresponds to the 450 nm absorption of one of Its derivatives... [Pg.565]

Compounds having the 16,17 ketal, eg, budesonide, amcinonide, fluocinonide, halcinonide, triamcinolone acetonide, and flurandrenohde, also undergo metabohsm by routes that parahel that of cortisol metabohsm. Unsymmetrical acetals such as budesonide are also metabolized by routes not available to the more metabohcahy stable symmetrical 16a,17a-isopropyhdiene-dioxysubstituted compounds (desonide, flunisohde, and triamcinolone acetonide). Isozymes within the cytochrome P450 3A subfamily are thought to catalyze the metabohsm of budesonide, resulting in formation of 16a-hydroxyprednisolone and 6P-hydroxybudesonide (19,20) (Fig. 3) in addition to the more common metabohc steps (oxidation via reduction of A, etc). [Pg.97]

As a class of compounds, the two main toxicity concerns for nitriles are acute lethality and osteolathyrsm. A comprehensive review of the toxicity of nitriles, including detailed discussion of biochemical mechanisms of toxicity and stmcture-activity relationships, is available (12). Nitriles vary broadly in their abiUty to cause acute lethaUty and subde differences in stmcture can greatly affect toxic potency. The biochemical basis of their acute toxicity is related to their metaboHsm in the body. Following exposure and absorption, nitriles are metabolized by cytochrome p450 enzymes in the Hver. The metaboHsm involves initial hydrogen abstraction resulting in the formation of a carbon radical, followed by hydroxylation of the carbon radical. MetaboHsm at the carbon atom adjacent (alpha) to the cyano group would yield a cyanohydrin metaboHte, which decomposes readily in the body to produce cyanide. Hydroxylation at other carbon positions in the nitrile does not result in cyanide release. [Pg.218]

Many enzymes have been the subject of protein engineering studies, including several that are important in medicine and industry, eg, lysozyme, trypsin, and cytochrome P450. SubtiHsin, a bacterial serine protease used in detergents, foods, and the manufacture of leather goods, has been particularly well studied (68). This emphasis is in part owing to the wealth of stmctural and mechanistic information that is available for this enzyme. [Pg.203]

Xenobiotics metabolism, 1, 223-225 monooxygenation cytochrome P450 in, 1, 259-260 Xenon... [Pg.925]

S Modi, MI Paine, MI Sutcliffe, L-Y Lian, WU Pnmi-ose, CR Wolfe, GCK Roberts. A model for human cytochrome P450 2d6 based on homology modeling and NMR studies of substrate binding. Biochemistry 35 4540-4550, 1996. [Pg.311]

Combined chemotherapy/gene therapy of tumors based on activation of antitumor preparations with cytochromes P450 99MI38. [Pg.232]

Cyclic adenosine monophosphate, 25f Cyclic adenosine monophosphate response element binding, 83, 88 Cytochrome P450 enzymes, 171... [Pg.294]

Cytochrome P450 monooxygenases are characterized through the presence of the heme (protoporphyrin IX) prosthetic group (Scheme 10.1) that is coordinated to the enzyme through a conserved cysteine ligand. They have obtained their name from the signature absorption band with a maximum near 450 nm in the difference spectrum when incubated with CO. The absorption arises from the Soret Jilt transition of the ferrous protoporphyrin IX-CO complex. [Pg.350]

The overall hydroxylation or epoxidation reaction catalyzed by cytochrome P450s involves the insertion of one oxygen atom, derived from molecular oxygen, into a C-H bond or into the Jt-system of an olefin, with the concomitant reduction of the... [Pg.350]

Scheme 10.3 Electron-transport systems associated with cytochrome P450 monooxygenases. Arrows indicate electron transfer. Scheme 10.3 Electron-transport systems associated with cytochrome P450 monooxygenases. Arrows indicate electron transfer.
Scheme 10.4 The catalytic cycle of cytochrome P450. Only one possible valence structure of the oxoferrous species IV has been depicted for clarity. See text for details. Scheme 10.4 The catalytic cycle of cytochrome P450. Only one possible valence structure of the oxoferrous species IV has been depicted for clarity. See text for details.
Scheme 10.5 Tentative mechanism for cytochrome P450-cata-lyzed epoxidation of a double bond. The reactive iron-oxo species VII (see Scheme 10.4) reacts with the olefin to give a charge transfer (CT) complex. This complex then resolves into the epoxide either through a radical or through a cationic intermediate. Scheme 10.5 Tentative mechanism for cytochrome P450-cata-lyzed epoxidation of a double bond. The reactive iron-oxo species VII (see Scheme 10.4) reacts with the olefin to give a charge transfer (CT) complex. This complex then resolves into the epoxide either through a radical or through a cationic intermediate.
Cytochrome P450 enzymes have been the subject of a number of recent reviews in which their mechanism and scope of action are covered in much detail [1, 6, 10, 11]. The reader is referred to these articles for a more thorough account of the mechanism and reactivity of cytochrome P450 enzymes, while we present a few representative examples of cytochrome P450-catalyzed epoxidation below. The enzymes we chose are all involved in the biosynthesis of polyketide natural products. Polyketides are a large, structurally diverse family of compounds and have provided a wealth of therapeutically useful drugs and drug leads. [Pg.355]

Scheme 10.6 Byproducts of cytochrome P450 oxygenase catalyzed epoxidation. Top N-alkylation of the porphyrin ring. Bottom group migration to give aldehydes. [Pg.356]


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Activation cytochrome P450 biotransformations

Alkanes cytochrome P450 bacteria

Antipsychotic drugs cytochrome P450 metabolism

Benzene cytochrome P450 hydroxylation

Benzo pyrene cytochrome P450 biotransformations

Bioactivation cytochrome P450-mediated

Biomarkers cytochrome P450 induction

Biooxidation cytochrome P450 monooxygenase

Biotransformations cytochrome P450 expressed

Brain cytochrome p450 distribution

Camphor cytochrome P450 hydroxylation

Citalopram cytochrome P450 inhibition

Coumarin anticoagulants cytochrome P450

Cysteine Cytochrome P450-dependent

Cytochrome P450 (CYP

Cytochrome P450 (CYP isoforms

Cytochrome P450 (CYP monooxygenases

Cytochrome P450 CYP1A1, induction

Cytochrome P450 CYP1A2, induction

Cytochrome P450 Mono-oxygenases

Cytochrome P450 activity

Cytochrome P450 activity biotransformation

Cytochrome P450 aromatase

Cytochrome P450 catalysis

Cytochrome P450 classification

Cytochrome P450 complex

Cytochrome P450 dependent monoxygenase

Cytochrome P450 distribution

Cytochrome P450 electron transport system

Cytochrome P450 enzyme CYP3A4, inhibition

Cytochrome P450 enzyme family

Cytochrome P450 enzyme function

Cytochrome P450 enzyme system

Cytochrome P450 enzyme system drugs affecting

Cytochrome P450 enzyme system metabolism

Cytochrome P450 enzymes

Cytochrome P450 enzymes (CYP

Cytochrome P450 enzymes Monooxygenases

Cytochrome P450 enzymes Subject

Cytochrome P450 enzymes alcohol metabolism

Cytochrome P450 enzymes antidepressant drugs

Cytochrome P450 enzymes blockers

Cytochrome P450 enzymes drug metabolism

Cytochrome P450 enzymes gene families

Cytochrome P450 enzymes gene polymorphisms

Cytochrome P450 enzymes induction

Cytochrome P450 enzymes induction/inhibition

Cytochrome P450 enzymes inhibition

Cytochrome P450 enzymes inhibitors

Cytochrome P450 enzymes intermediate metabolizers

Cytochrome P450 enzymes locations

Cytochrome P450 enzymes metabolic activation

Cytochrome P450 enzymes naming

Cytochrome P450 enzymes pharmacogenetic differences

Cytochrome P450 enzymes pharmacokinetics

Cytochrome P450 enzymes poor metabolizers

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Cytochrome P450 enzymes reactive intermediates activated

Cytochrome P450 enzymes reductive metabolism

Cytochrome P450 enzymes reductive transformations

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Cytochrome P450 enzymes steroid biosynthesis

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Cytochrome P450 enzymes, phylogenetic

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Cytochrome P450 inhibition

Cytochrome P450 inhibition assay

Cytochrome P450 inhibitor

Cytochrome P450 interactions

Cytochrome P450 irreversible

Cytochrome P450 isoenzyme inducers

Cytochrome P450 isoenzyme inducers Tacrolimus

Cytochrome P450 isoenzyme inhibitors

Cytochrome P450 isoenzyme substrates

Cytochrome P450 isoenzyme substrates Protease inhibitors

Cytochrome P450 isoenzymes

Cytochrome P450 isoenzymes drug metabolism

Cytochrome P450 isoenzymes drugs metabolized

Cytochrome P450 isoenzymes genetic polymorphism

Cytochrome P450 isoenzymes oxidative reactions

Cytochrome P450 isoforms

Cytochrome P450 isozymes

Cytochrome P450 kinetic parameters

Cytochrome P450 liability

Cytochrome P450 liver enzymes induction

Cytochrome P450 liver enzymes metabolism

Cytochrome P450 liver enzymes transporter

Cytochrome P450 metabolizing enzymes

Cytochrome P450 mimics

Cytochrome P450 models

Cytochrome P450 monooxygenase

Cytochrome P450 monooxygenase systems

Cytochrome P450 monooxygenase yeast

Cytochrome P450 monooxygenases

Cytochrome P450 monooxygenases chirality

Cytochrome P450 monooxygenases forms

Cytochrome P450 monooxygenases herbicides

Cytochrome P450 monooxygenases induction

Cytochrome P450 monooxygenases inhibitors

Cytochrome P450 monooxygenases metabolism

Cytochrome P450 monooxygenases species differences

Cytochrome P450 multiplicity

Cytochrome P450 mutant

Cytochrome P450 nomenclature

Cytochrome P450 oxidases

Cytochrome P450 oxidation reactions

Cytochrome P450 oxidoreductase

Cytochrome P450 oxidoreductase (POR

Cytochrome P450 oxygenase

Cytochrome P450 protein

Cytochrome P450 purification

Cytochrome P450 reactions

Cytochrome P450 reductase

Cytochrome P450 reductase Class

Cytochrome P450 reductase antibodies

Cytochrome P450 reductase diversity

Cytochrome P450 reductase domains

Cytochrome P450 reductase electron transfer rates

Cytochrome P450 reductase expression systems

Cytochrome P450 reductase fungal

Cytochrome P450 reductase fusion proteins with

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Cytochrome P450 reductase mutagenesis

Cytochrome P450 reductase plant

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Cytochrome P450 reductase ratio

Cytochrome P450 reductase redox properties

Cytochrome P450 reductase structure

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Cytochrome P450 side chain cleavage enzyme

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Cytochrome P450 superfamily

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Cytochrome P450 system antidepressants

Cytochrome P450 system benzodiazepines

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Cytochrome P450 system mitochondrial

Cytochrome P450 system phenobarbital

Cytochrome P450, catalysis, electron

Cytochrome P450, catalysis, electron transfer

Cytochrome P450, electron-transfer

Cytochrome P450, electron-transfer reactions

Cytochrome P450, hepatic microsomal

Cytochrome P450, xenobiotic-metabolizing

Cytochrome P450, xenobiotic-metabolizing cultured cells

Cytochrome P450, xenobiotic-metabolizing expression systems

Cytochrome P450, xenobiotic-metabolizing system

Cytochrome P450-based drug

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Cytochrome P450-camphor

Cytochrome P450-dependent

Cytochrome P450-dependent microsomal

Cytochrome P450-dependent monooxygenases

Cytochrome P450-mediated hepatic metabolism

Cytochrome P450-mediated metabolism

Cytochrome P450s

Cytochrome P450s

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Cytochrome P450s, their multiple forms

Cytochrome interaction with P450 reductase

Cytochromes P450 alterations

Cytochromes P450 brain

Cytochromes P450 decreased activity

Cytochromes P450 epoxidation reactions

Cytochromes P450 increased activity

Cytochromes P450 origins

Cytochromes P450 oxygenation

Cytochromes P450 polymorphisms

Cytochromes P450 regulation

Cytochromes P450 structure

Cytochromes P450 substrate binding

Cytochromes P450 tissue distribution

Cytochromes P450, oxidation

Dealkylation cytochrome P450 biotransformations

Detoxication cytochrome P450 enzymes

Direct Cytochrome P450 Inhibition

Drug biotransformation enzyme systems, cytochromes P450

Drug cytochrome P450 family

Drugs cytochrome P450-mediated

Electron Transfer to P450s from Cytochrome

Epoxidation cytochrome P450 biotransformations

Ethnic differences cytochrome P450 enzymes

Evolution cytochrome P450 enzymes

Flavonoids cytochrome P450 monooxygenase

Fluoxetine cytochrome P450 inhibition

Fluvoxamine cytochrome P450 inhibition

Heme cytochrome P450

Hepatic cytochrome P450 enzymes

Hormonal Regulation of Liver Cytochrome P450 Enzymes

Human Cytochrome P450 Enzymes

Hydroxylation cytochrome P450 biotransformations

Hydroxylation cytochrome P450 monooxygenase system

Ligand Conformational Equilibrium in a Cytochrome P450 Complex

Liver cytochrome P450 enzymes

Liver cytochrome P450 hydroxylation

Liver cytochrome P450 hydroxylation models

Liver cytochrome P450 isoforms

Metabolism cytochrome P450 metabolizing enzymes

Monooxygenase cytochrome P450-dependent

Monooxygenases Cytochrome P450 system

Mutation cytochrome P450 monooxygenase

NADPH-Cytochrome P450 Reductase (CPR)

NADPH-cytochrome P450 enzymes

NADPH/cytochrome P450 reductase

Nuclear Receptor Regulation of Hepatic Cytochrome P450 Enzymes

Oxidases Cytochrome P450 system

Oxidation cytochrome P450 biotransformations

Oxidation cytochrome P450 enzymes

Oxidation cytochrome P450 monooxygenases

Oxygen cytochrome P450 biotransformations

Oxygen cytochrome P450 monooxygenation

Oxygen cytochrome P450, methane

P450 cytochrome curcumin

P450 cytochrome resveratrol

P450 cytochrome xenobiotic metabolism

P450-linked cytochrome oxidase

Paroxetine cytochrome P450 inhibition

Resistance cytochrome P450 studies

Sertraline cytochrome P450 inhibition

Structures of Cytochrome P450 Enzymes

Time-dependent cytochrome P450

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