Microsomes and Drug Oxidations

Contents

List of Participants

Preface

Otto Rosenthal, the Man and His Work

I Biochemistry

Lipid Structure of Liver Microsomal Membranes, Limitations of a Model

A Study of Cytochrome P-450 Reduction by Sodium Dithionite

Investigation of Microsomal Hydroxylating System at Sub-Zero Temperatures

Isolation of Microsomal Electron Transport Components and Reconstitution of the Electron Transfer Activity on Liposomal Vesicles

Differences in Substrate Affinity and Catalytic Specificity of Inducible and Non-Inducible Forms of Cytochrome P-450 in Rabbit Liver

Effects of Buffer Composition on the Low-Spin ESR Spectrum of Cytochrome P-450

Kinetics of TiamutinR Interaction with Cytochrome P-450 from Rabbit Liver

Different Phases of Hydroxylase Induction in Liver

Microsomes of Female Mice during Inhalation of Cyclohexane and D,L-Camphor

Protein-Lipid Interactions in the Liver Microsomal Hydroxylase System

Further Studies of the Fluroxene Mediated Destruction of Hepatic Microsomal Cytochromes P-450 in Vitro

Purification of Membrane-Bound Oxygenases: Isolation of two Electrophoretically Homogeneous Forms of Liver Microsomal Cytochrome P-450

Microsomal Hemeproteins P-450LM-2 and P-450LM4 : Comparative Structural Studies

Hepatic Microsomal Ethanol Oxidizing System: Isolation and Reconstitution

Characterization of NADPH-Cytochrome c (P-450) Reductase Purified by Biospecific Affinity Chromatography Utilizing Spectrophotometric and Electron Paramegnetic Resonance Techniques

Relationship between the Membrane Lipids and Substrate-Cytochrome P-450 Binding Reaction in Bovine Adreno-Cortical Microsomes

Kinetic and Spectral Evidence for Multiple Species of Cytochrome P-450 in Liver Microsomes

Differences in the Interactions of R and S Warfarin with Hepatic Microsomal Cytochrome P-450

Multiple Forms of Housefly Cytochrome P-450

Catalytic Hydroxylation Activities and Some Other Properties of Partially Purified Rabbit Pulmonary Microsomal Cytochrome P-450

Hepatic Microsomal and Solubilized Mixed-Function Oxidase Systems from the Little Skate, Raja erinaoea, A Marine Elasmobranch

Aminimide Polymers as Supports for Affinity Chromatography, Under Low and High Pressure, of Microsomal Enzymes

Sex Differences in the Pattern of Cytochromes P-450 in Rat Liver Microsomes

Characterization of Multiple Forms of Highly Purified Cytochrome P-450 from the Liver Microsomes of Rats, Mice and Rabbits

The Mechanism of Cytochrome P-450 Action

Oxygen Reactions of the P-450 Heme Protein

The Peroxidase Nature of Cytochrome P-450

Cytochrome P-450 Catalyzed Oxene Transfer from Various Donors

Association of Type I, Type II, and Reverse Type I Difference Spectra with Absolute Spin State of Cytochrome P-450 Iron

NMR Relaxation Time Studies of Substrate Interactions with P-450 and other Hemoproteins

The Interaction of Polyhalogenated Methanes with Ferrous Cytochrome P-450

Substrate-Elicited Dissociation of the Isosafrole Metabolite-Cytochrome P-450 Complex and the Consequential Reactivation of Monooxygenation

The Interaction of Halothane with Liver Microsomal Cytochrome P-450

The Formation of Hydrogen Peroxide During Hepatic Microsomal Electron Transport Reactions

Oxygen Transfer in Microsomal Oxidative Desulfuration

Redox and Ligand Dynamics in P~450cam - Putidaredoxin Complexes

The Inhibition of Mixed-Function Oxidation Reactions by Amphetamines in Liver and Lung Microsomes

The Physiological Implications of Drug Oxidations to the Cell

Nicotinamide Nucleotide Systems and Drug Oxidation in the Liver Cell

The Role of Reducing Equivalents Generated in Mitochondria in Hepatic Mixed-Function Oxidation

Destruction of Cytochrome P-450 by Linoleic Acid Hydroperoxide

Stoichiometry of Oxygen Uptake, NADPH Oxidation and Ethylmorphine N-Demethylation by Hepatic Microsomes

Structural and Functional Interaction of Rough Endoplasmic Reticulum (RER) and Mitochondria during Synthesis of Hepatic Cytochrome P-450

Mechanism of N-Oxide Formation by Hepatic Mixed Function Oxidases

A Preliminary Comparative Study on the Influence of Cysteamine and Metyrapone on Mixed-Function Oxygenase Activities in Variously Pretreated Liver Microsomes from Rats and Mice

Inhibition of Rat Liver Microsomal DT Diaphorase by Benzo (a) Pyrene Metabolite(S)

Characteristics of the Hepatic Monooxygenase Catalyzing the Metabolism of Prostaglandin A1 (PGA1) in Guinea Pigs and Rats. I. Effects of Inducers

Studies on a Cytochrome P-450-Dependent Hydroxylase System Active on Steroids in Bacillus Megaterium

II Pharmacology

Impact of Drug Monoxygenases in Clinical Pharmacology

Role of Liver Nuclei in the Formation of DNA Binding Products from Benzo (a) Pyrene

Mechanism of Microsomal Activation of Benzo (a) Pyrene to Diol-Epoxides: The Separation and Characterization of Intermediates and Products

The Metabolism of Benzo (a) Pyrene in Cell Cultures and Homogenates from Different Human Fetal Tissues

Aryl Hydrocarbon Hydroxylase in Cultured Human Lymphocytes

Assignment of a Human Gene for Aryl Hydrocarbon Hydroxylase Expression to Chromosome 2

Oxidative Metabolism of Carcinogens by Trout Liver Resulting in Protein Binding and Mutagenicity

Drug-Drug Interactions via Inhibition of Microsomal Enzymes Involved in Metabolism of Epoxides Produced by Microsomal Monooxygenase

Levels of Glutathione and Glutathione-Metabolizing Enzymes in Rat Lung

The Disposition of Benzo (a) Pyrene in Isolated Perfused Rat Lung

Epoxide Hydratase in Rat Lung

Monooxygenase Catalyzed Activation of Thiono-Sulfur Containing Compounds to Reactive Intermediates

Stimulatory Effects of Polychlorinated Biphenyls (PCB) on Cytochromes P-450 and P-448 Mediated Microsomal Oxidations

Depression of Hepatic Cytochrome P-450-dependent Monooxygenase Systems with Administered Interferon Inducing Agents

Alterations of Hepatic Microsomal Mixed Function Oxygenase Dependent H2O2 Formation due to "Uncoupling" and Induction as Demonstrated in vivo by Elimination Kinetics of Ethanol in Guinea Pig

The Microsomal Metabolism of Carcinogenic and/or Therapeutic Hydrazines

Role of Hydroxylated Metabolites of Phenytoin in Dose-Dependency

Species Differences in Drug Metabolism: in vivo Parameters of Hepatic Drug-Metabolising Enzyme Activity in the Baboon

Evidence for Binding of Lidocaine to Two Catalytically Different Sites of Liver Microsomal Cytochrome P-450

Differential Influence of Physiological, Pharmacological and Pathological Alterations on Hepatic and Entrahepatic Drug Metabolism

Metabolism of Hexobarbital Enantiomers and Interaction with Cytochrome P-450 in Male and Female Mice and Rats

The Mechanism of Degradation of Endogenous Heme and Cytochrome P-450 by Heme Oxygenase

Induction of Cytochrome P-448 by 3-Methylcholanthrene in the Rat during Inhibition of Protein Synthesis in Vivo

Stimulation of Liver Growth and Mixed-Function Oxidase by a-Hexachlorocyclohexane: Separation of Inductive Pathways

Induction of Cytochrome P-450 by Long-Term Infusion of Phenobarbital

Metabolism and Mutagenicity of 2-Acylaminofluorenes and Related Compounds

In Vivo Parameters of Drug Metabolism - Differences in Specificity Towards Inducing Agents

Studies on the Mechanism by which Disulfiram and Diethyldithiocarbamate Affect Drug Metabolism

Alterations in the Activities of Drug Metabolizing Enzymes in Rat Liver Microsomes by Dietary and in Vitro Incorporated Cholesterol

Steroid - 16α-Hydroxylase in Rat Liver: Biochemical and Biological Properties

Correlation between Drug, Lipid and Carbohydrate Metabolism in the Rat after Chronic Beta-Adrenoreceptor Antagonist Treatment

Conversion of Trichloroethylene to Carbon Monoxide by Microsomal Cytochrome P-450

Stereoselective in Vitro Aromatic Oxygenation of Chiral 1,4-Benzodiazepin-2-Ones

Effects of Disease States on Drug Disposition in Man

Isolation of Rat Liver Epoxide Hydratase: Properties and Substrate Specificity of the Pure Enzyme

Reduction of a Tertiary Amine N-Oxide and an Arene Oxide in Relation to the Reduction Rate of Cytochrome P-450 in Rat Liver Microsomes

Microsomal Oxidation of Isoproterenol and Irreversible Protein Binding of Metabolites

Benzo (a) Pyrene Metabolism by Microsomes and Isolated Epithelial Cells from Rat Small Intestine

Characterization of the Drug Monooxygenase System in Mouse Small Intestine

Formation of Alkylation and Carbamylation Intermediates and Cytochrome P-450 Catalyzed Monooxygenation of the 2-Chloroethylnitrosoureas CCNU and Methyl CCNU

Proposed Mechanism for the Reductive Glycosidic Cleavage of Daunomycin (NSC 82151) and Adriamycin (NSC 123127)

Covalent Binding of Styrene Oxide to Rat Liver Macro-Molecules in Vivo and in Vitro

III Outlook

The Regulation of Human Drug Metabolism by Nutritional Factors

The Bay-Region Theory: A Quantum Mechanical Approach to Aromatic Hydrocarbon-Induced Carcinogenicity

The Activation and Induction of Biphenyl Hydroxylation and Chemical Carcinogenesis

Integrated Electron Transfer: Iron States and Regulation

Purification of Liver Microsomal Cytochrome P-450: Hopes and Promises

Active Oxygen - Fact or Fancy

Index