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Arachidonate metabolism
Stable Identifier
R-HSA-2142753
DOI
10.3180/REACT_147851.2
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Metabolism (Homo sapiens)
Metabolism of lipids (Homo sapiens)
Fatty acid metabolism (Homo sapiens)
Arachidonate metabolism (Homo sapiens)
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Eicosanoids, oxygenated, 20-carbon fatty acids, are autocrine and paracrine signaling molecules that modulate physiological processes including pain, fever, inflammation, blood clot formation, smooth muscle contraction and relaxation, and the release of gastric acid. Eicosanoids are synthesized in humans primarily from arachidonate (all-cis 5,8,11,14-eicosatetraenoate) that is released from membrane phospholipids. Once released, arachidonate is acted on by prostaglandin G/H synthases (PTGS, also known as cyclooxygenases (COX)) to form prostaglandins and thromboxanes, by arachidonate lipoxygenases (ALOX) to form leukotrienes, epoxygenases (cytochrome P450s and epoxide hydrolase) to form epoxides such as 15-eicosatetraenoic acids, and omega-hydrolases (cytochrome P450s) to form hydroxyeicosatetraenoates (Buczynski et al. 2009, Vance & Vance 2008).
Levels of free arachidonate in the cell are normally very low so the rate of synthesis of eicosanoids is determined primarily by the activity of phospholipase A2, which mediates phospholipid cleavage to generate free arachidonate. The enzymes involved in arachidonate metabolism are typically constitutively expressed so the subset of these enzymes expressed by a cell determines the range of eicosanoids it can synthesize.
Eicosanoids are unstable, undergoing conversion to inactive forms with half-times under physiological conditions of seconds or minutes. Many of these reactions appear to be spontaneous.
Literature References
PubMed ID
Title
Journal
Year
19244215
Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology
Dumlao, DS
,
Buczynski, MW
,
Dennis, EA
J Lipid Res
2009
Biochemistry of Lipids, Lipoproteins and Membranes, 5th Edition
Vance, JE
,
Vance, DE
2008
Participants
Events
PLA2G4A (cPLA2) hydrolyzes phosphatidylcholine
(Homo sapiens)
SLC27A1 transports arachidonate across the ER membrane
(Homo sapiens)
AWAT1 transfers acyl group from acyl-CoA to ARACOH, forming wax esters
(Homo sapiens)
FAAH hydrolyses AEA to AA and ETA
(Homo sapiens)
FAAH2 hydrolyses AEA to AA and ETA
(Homo sapiens)
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
(Homo sapiens)
Synthesis of Leukotrienes (LT) and Eoxins (EX)
(Homo sapiens)
Synthesis of 5-eicosatetraenoic acids
(Homo sapiens)
Synthesis of 15-eicosatetraenoic acid derivatives
(Homo sapiens)
Synthesis of 12-eicosatetraenoic acid derivatives
(Homo sapiens)
Synthesis of Hepoxilins (HX) and Trioxilins (TrX)
(Homo sapiens)
Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE)
(Homo sapiens)
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)
(Homo sapiens)
Participates
as an event of
Fatty acid metabolism (Homo sapiens)
Event Information
Go Biological Process
arachidonate metabolic process (0019369)
Orthologous Events
Arachidonate metabolism (Bos taurus)
Arachidonate metabolism (Caenorhabditis elegans)
Arachidonate metabolism (Canis familiaris)
Arachidonate metabolism (Danio rerio)
Arachidonate metabolism (Dictyostelium discoideum)
Arachidonate metabolism (Drosophila melanogaster)
Arachidonate metabolism (Gallus gallus)
Arachidonate metabolism (Mus musculus)
Arachidonate metabolism (Plasmodium falciparum)
Arachidonate metabolism (Rattus norvegicus)
Arachidonate metabolism (Saccharomyces cerevisiae)
Arachidonate metabolism (Schizosaccharomyces pombe)
Arachidonate metabolism (Sus scrofa)
Arachidonate metabolism (Xenopus tropicalis)
Authored
Williams, MG (2012-02-24)
Reviewed
Rush, MG (2012-11-10)
Created
Williams, MG (2012-02-24)
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