Lipoxygenases and Their Products - 1st Edition - ISBN: 9780121978006, 9780323156530

Lipoxygenases and Their Products

1st Edition

Editors: Stanley Crooke
eBook ISBN: 9780323156530
Imprint: Academic Press
Published Date: 28th March 1991
Page Count: 312
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Lipoxygenases and Their Products provides a cogent summary of the advances in understanding lipoxygenases and their products, emphasizing their pharmacology and pathophysiology; regulation and structure; physiological role; and receptors and receptor antagonists. This text also reviews the literature where specific receptor antagonists (as opposed to enzymatic inhibitors) have been used to characterize the pharmacologic action and the pathophysiologic roles of some of lipoxygenase products of arachidonic acid metabolism. This book is organized into 11 chapters and begins with an overview of the biochemical, pharmacological, and pathophysiological aspects of 5-lipoxygenase products of arachidonic acid metabolism in the respiratory, cardiovascular, renal, gastrointestinal, and central nervous systems. The discussion then shifts to human 5-lipoxygenase, emphasizing this enzyme purification, stimulatory factors, and membrane translocation. The reader is methodically introduced to 5-lipoxygenase activity in rats and pigs; the potential and therapeutic value of 5-lipoxygenase inhibitors; the distribution of 15-lipoxygenase in cells or tissues; and products formed through the 15-lipoxygenase pathway. This book also considers lipoxins and third-generation peptidoleukotriene receptor antagonists, and then concludes with a summary of the physiological and pathophysiological effects of leukotrienes and lipoxins in a variety of organs. This book is of interest to scientists interested in arachidonic acid and its metabolites, to scientists engaged in drug discovery-and-development activities in academia and the pharmaceutical industry, and to clinicians interested in diseases associated with leukotrienes and related products.

Table of Contents



Chapter 1 Pharmacology and Pathophysiology of 5-Lipoxygenase Products

I. Introduction

II. Respiratory System

III. Cardiovascular System

IV. Renal System

V. Gastrointestinal System

VI. Central Nervous System

VII. Conclusions


Chapter 2 Regulation and Structure of Human Leukocyte 5-Lipoxygenase

I. Introduction

II. Purification of Human 5-Lipoxygenase

III. Stimulatory Factors for Human 5-Lipoxygenase

IV. LTA4 Synthase Activity of Human 5-Lipoxygenase

V. Cloning the Gene for Human 5-Lipoxygenase

VI. Expression of Cloned Human Leukocyte 5-Lipoxygenase

VII. Membrane Translocation of Human 5-Lipoxygenase

VIII. Summary and Conclusions


Chapter 3 Regulation of 5-Lipoxygenase Activity in Rat Basophilic Leukemia Cells

I. Introduction

II. Enzyme Cofactors

III. Leukotriene Synthesis and Membrane Translocation of 5-Lipoxygenase in RBL-2H3 Cells

IV. Conclusions


Chapter 4 Arachidonate 5-Lipoxygenase of Porcine Leukocytes Studied Using Its Monoclonal Antibodies

I. Purification of 5-Lipoxygenase

II. Selective Inhibitors of 5-Lipoxygenase

III. Catalytic Properties of 5-Lipoxygenase

IV. Lipoxin Synthesis by 5-Lipoxygenase

V. Enzyme Immunoassays for Lipoxygenase

VI. Subcellular Localization of Lipoxygenase

VII. Conclusions


Chapter 5 Enzymatic Studies on Purified 5-Lipoxygenase

I. Introduction

II. Purification

III. Assay

IV. Physical and Structural Properties

V. Kinetic Properties

VI. The LTA4 Synthase Activity of 5-LO

VII. Issues


Chapter 6 Potential and Therapeutic Value of Development of Novel 5-Lipoxygenase Inhibitors

I. Introduction

II. Development of 5-Lipoxygenase Inhibitors

III. Evidence for Leukotriene Involvement on Human Disease

IV. Evidence for Leukotriene Involvement from Preclinical Models

V. Conclusions


Chapter 7 Physiological Role of the 15-Lipoxygenase

I. Introduction

II. Cellular or Tissue Distribution of 15-Lipoxygenase

III. Products Formed via the 15-Lipoxygenase Pathway

IV. Action of 15-Lipoxygenase on Membranes and HETEs

V. Biological Effects of 15-Lipoxygenase Pathway Products

VI. 15-Lipoxygenase Metabolites as Enzyme Substrates


Chapter 8 Receptors and Receptor Antagonists for Mammalian 5-Lipoxygenase Products

I. Introduction

II. Leukotriene A4 Transcellular Metabolism

III. LTB4 Receptor Biology

IV. LTC4-Mediated Cellular Responses

V. LTD4 Receptor Biology

VI. LTE4 as a Partial Agonist

VII. The Implication of Leukotriene Molecular Pharmacology


Chapter 9 Third-Generation Peptidoleukotriene Receptor Antagonists

I. Introduction

II. SK&F 104353 and SK&F 106203

III. ICI 198,615 and ICI 204,219

IV. L-660,711 (MK-571)

V. Conclusions


Chapter 10 Lipoxins: Bioactive Lipoxygenase Interaction Products

I. Introduction

II. Biochemistry

III. Biological Activities

IV. Conclusions


Chapter 11 Perspectives

I. Introduction

II. The Role of Products of 5-Lipoxygenase

III. The Role of 5-Lipoxygenase

IV. Development of Drugs That Inhibit 5-Lipoxygenase or the Effects of Its Products

V. Current Research Opportunities

VI. Current Drug Discovery Opportunities

VII. Drug Discovery Risks

VIII. Conclusions Relevant to Drug Discovery




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© Academic Press 1991
Academic Press
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About the Editor

Stanley Crooke

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