Enzymatic Reactions in Leukotriene Biosynthesis
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Authors
Kane, Kevin R.
Issue Date
1984
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
The leukotrienes are a family of polyunsaturated fatty acid metabolites of
arachidonic acid. Leukotrienes are known to be the active components of the so-called
slow-reacting substance of anaphylaxis (SRS-A). They are potent
spasmogens which greatly intensify the effects of an acute allergic reaction. As
such, they have been implicated in asthmatic symptoms as well as inflammatory
responses of the body. Modulation or inhibition of leukotriene formation may be a
useful tool in treating diseases of hypersensitivity such as asthma and allergies, but
a methodical approach to finding such a method of modulation suggests the need to
be certain of structures and biosynthetic pathways involved in leukotriene
production. Recently the structures of the various leukotrienes have been
elucidated and a biosynthetic route for their production from arachicbnic acid
postulated. However, there exist few reliable methods for quantitatively, extracting and detecting leukotrienes from biological samples. In addition, much of
the work with leukotriene biosynthesis has involved use of rat basophilic leukemia-
1 cells as a model system, since they can be obtained rather easily and
inexpensively in large quantities when needed, factors which have precluded use of
human polymorphonuclear leukocytes in many studies. The purpose of this study was to investigate further methods for extraction
and chromatography of leukotrienes and use them to investigate leukotriene
production by human PMNLs and subsequently attempt to characterize the
biosynthetic pathway of leukotriene formation therein. Leukotriene production by
human PMNLs after stimulation with calcium ionophore A23187 was investigated
as one segment of this project. In addition, the hypothesized biological
intermediates of the leukotriene pathway were incubated in the presence of broken
cell preparations containing the enzymes responsible for leukotriene production.
Using reverse phase high performance liquid chromatography and extraction
procedures tested initially, the products of interest of these reactions were
separated, identified and quatitated, yielding support for the proposed biosynthetic
pathway of leukotrienes, as well as giving some insight into the competing
enzymatic and non-enzymatic reactions which take place.
Description
ix, 62 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder. All rights reserved.