Lipoxygenases and Their Products

Lipoxygenases and Their Products

1st Edition - March 28, 1991

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  • Editor: Stanley Crooke
  • eBook ISBN: 9780323156530

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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

  • Contributors


    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



Product details

  • No. of pages: 312
  • Language: English
  • Copyright: © Academic Press 1991
  • Published: March 28, 1991
  • Imprint: Academic Press
  • eBook ISBN: 9780323156530

About the Editor

Stanley Crooke

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