Arachidonate 5-lipoxygenase-activating protein also known as 5-lipoxygenase activating protein, or FLAP, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''ALOX5AP''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
FLAP is necessary for the activation of
5-lipoxygenase
Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme (EC 1.13.11.34) that in humans is encoded by the ''ALOX5'' gene. Arachidonate 5-lipoxygenase is a member of the lipoxygenase fa ...
and therefore for the production of
leukotriene
Leukotrienes are a family of eicosanoid inflammation, inflammatory mediators produced in leukocytes by the redox, oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxyg ...
s,
5-hydroxyeicosatetraenoic acid
5-Hydroxyeicosatetraenoic acid (5-HETE, 5(''S'')-HETE, or 5''S''-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid. It is produced by diverse cell types in humans and other animal species. These cells may then metabolize the formed 5(' ...
,
5-oxo-eicosatetraenoic acid, and
specialized pro-resolving mediators
Specialization or Specialized may refer to:
Academia
* Academic specialization, may be a course of study or major at an academic institution or may refer to the field in which a specialist practices
* Specialty (medicine), a branch of medical ...
of the
lipoxin
A lipoxin (LX or Lx), an acronym for lipoxygenase interaction product, is a bioactive autacoid metabolite of arachidonic acid made by various cell types. They are categorized as nonclassic eicosanoids and members of the specialized pro-resolvi ...
and
resolvin
Resolvins are specialized pro-resolving mediators (SPMs) derived from omega-3 fatty acids, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as from two isomers of docosapentaenoic acid (DPA), one omega-3 and one ...
classes.
It is an integral protein within the nuclear membrane. FLAP is necessary in synthesis of leukotriene, which are lipid mediators of inflammation that is involved in respiratory and cardiovascular diseases. FLAP functions as a membrane anchor for 5-lipooxygenase and as an amine acid-bind protein. How FLAP activates 5-lipooxygenase is not completely understood, but there is a physical interaction between the two. FLAP structure consists of 4 transmembrane alpha helices, but they are found in
trimer forming a barrel. The barrel is about 60 Å high and 36 Å wide.
[;]
Clinical significance
Leukotrienes, which require the FLAP protein to be synthesized, have an established pathological role in allergic and respiratory diseases. Animal and human genetic evidence suggests they may also have an important role in atherosclerosis, myocardial infarction, and stroke. The structure of FLAP provides a tool for the development of novel therapies for respiratory and cardiovascular diseases and for the design of focused experiments to probe the cell biology of FLAP and its role in leukotriene biosynthesis.
Inhibitors
*
AM-679
*
MK-886
MK-886, or L-663536, is a leukotriene antagonist. It may perform this by blocking the 5-lipoxygenase activating protein (FLAP), thus inhibiting 5-lipoxygenase (5-LOX), and may help in treating atherosclerosis
Atherosclerosis is a pattern ...
* Veliflapon (BAY X1005)
References
Further reading
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External links
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{{DEFAULTSORT:5-Lipoxygenase-Activating Protein
Peripheral membrane proteins
Human proteins
Eicosanoids