5-Hydroxyeicosatetraenoic acid

5-HETE5-Hydroxyicosatetraenoic acid5-Hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid20-hydroxyeicosatetraenoic acid5-hydroperoxy-eicosatetraenoic acid
5-Hydroxyeicosatetraenoic acid (5-HETE, 5(S)-HETE, or 5S-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid.wikipedia
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5-Oxo-eicosatetraenoic acid

5-oxo-ETE
These cells may then metabolize the formed 5(S)-HETE to 5-oxo-eicosatetraenoic acid (5-oxo-ETE), 5(S),15(S)-dihydroxyeicosatetraenoic acid (5(S),15(S)-diHETE), or 5-oxo-15-hydroxyeicosatetraenoic acid (5-oxo-15(S)-HETE). Most importantly, 5-Hydroxyeicosanoid dehydrogenase (i.e. 5-HEDH) converts the 5-hydroxy residue of 5(S)-HETE to a ketone residue to form 5-oxo-eicosatetraenoic acid (i.e. 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoate, abbreviated as 5-oxo-ETE).
5-Oxo-eicosatetraenoic acid (i.e. 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid; also termed 5-oxo-ETE and 5-oxoETE) is a Nonclassic eicosanoid metabolite of arachidonic acid and the most potent naturally occurring member of the 5-HETE family of cell signaling agents.

Eicosanoid

eicosanoidsarachidonic acid derivativesEicosanoid Metabolism
5-Hydroxyeicosatetraenoic acid (5-HETE, 5(S)-HETE, or 5S-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid.
The enzyme 5-lipoxygenase (5-LO or ALOX5) converts arachidonic acid into 5-hydroperoxyeicosatetraenoic acid (5-HPETE), which may be released and rapidly reduced to 5-hydroxyeicosatetraenoic acid (5-HETE) by ubiquitous cellular glutathione-dependent peroxidases.

Oxoeicosanoid receptor 1

OXER1Oxoeicosanoid (OXE) receptor 1Oxoeicosanoid receptor
This 5(S)-HETE receptor is termed the oxoeicosanoid receptor 1 (abbreviated as (OXER1).
Oxoeicosanoid receptor 1 (OXER1) also known as G-protein coupled receptor 170 (GPR170) is a protein that in humans is encoded by the OXER1 gene located on human chromosome 2p21; it is the principle receptor for the 5-Hydroxyicosatetraenoic acid family of carboxy fatty acid metabolites derived from arachidonic acid.

Arachidonic acid

arachidonic acid metabolismarachidonatearachidonic
5-Hydroxyeicosatetraenoic acid (5-HETE, 5(S)-HETE, or 5S-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid.

Inflammation

inflammatoryinflammatory responseinflamed
Animal studies and a limited set of human studies suggest that this family of metabolites serve as hormone-like autocrine and paracrine signalling agents that contribute to the up-regulation of acute inflammatory and allergic responses.

5-Hydroxyeicosanoid dehydrogenase

Most importantly, 5-Hydroxyeicosanoid dehydrogenase (i.e. 5-HEDH) converts the 5-hydroxy residue of 5(S)-HETE to a ketone residue to form 5-oxo-eicosatetraenoic acid (i.e. 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoate, abbreviated as 5-oxo-ETE).
5-Hydroxyeicosanoid dehydrogenase (5-HEDH) or more formally, nicotinamide adenine dinucleotide phosphate (NADP + )-dependent dehydrogenase, is an enzyme that metabolizes an eicosanoid product of arachidonate 5-lipoxygenase (5-LOX), 5(S)-hydroxy-6S,8Z,11Z,14Z-eicosatetraenoic acid (i.e. 5-(S)-HETE; see 5-HETE) to its 5-keto analog, 5-oxo-eicosatetraenoic acid (i.e. 5-oxo-6S,8Z,11Z,14Z-eicosatetraenoic acid or 5-oxo-ETE).

Chemotaxis

chemotacticchemoattractantchemotactic factor
Biological activity was linked to it several years later when it was found to stimulate human neutrophil rises in cytosolic calcium, chemotaxis, and increases in their cell surface adhesiveness as indicated by their aggregation to each other.

Arachidonic acid 5-hydroperoxide

5-HPETE5-hydroperoxyeicosatetraenoic acidhydroxyeicosatetraenoic acid
ALOX5 metabolizes arachidonic acid to its hydroperoxide derivative, arachidonic acid 5-hydroperoxide i.e. 5S-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5(S)-HpETE).
The intermediate is then further metabolized to: a) leukotriene A4 which is then metabolized to the chemotactic factor for leukocytes, leukotriene B4, or to contractors of lung airways, leukotriene C4, leukotriene D4, and leukotriene E4; b) the leukocyte chemotactic factors, 5-Hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid; or c) the specialized pro-resolving mediators of inflammation, lipoxin A4 and lipoxin B4.

CYP4F3

Both variants localize on the endoplasmic reticulum and metabolize leukotriene B4 and very likely 5-hydroxyeicosatetraenoic acid, 5-oxo-eicosatetraenoic acid, and 12-hydroxyeicosatetraenoic acid by an omega oxidation reaction, i.e. by adding a hydroxyl residue to their terminal (i.e. C-20) carbon.

Lipoxin

lipoxinslipoxin A4Lipoxin B4
5-(S)-HETE family members share a common receptor target for stimulating cells that differs from the receptors targeted by the other major products of ALOX5, i.e., leukotriene B4, leukotriene C4, leukotriene D4, leukotriene E4, lipoxin A4, and lipoxin B4.
In the initial phases of many acute inflammatory responses, damaged tissues, invading pathogens, and other local events cause nearby cells to make and release arachidonic acid-derived pro-inflammatory metabolites such as: leukotrienes (LTs), e.g. LTB 4, LTB 4, LTC 4, LTD 4, and LTE 4 ; hydroxyeicosatetraenoic acids (HETEs), e.g. 5-HETE and 12-HETE; and oxoeicosanoids (oxo-ETE), e.g. 5-oxo-eicosatetraenoic acid (5-oxo-ETE) and 12-oxo-ETE.

Cytochrome P450

cytochrome P450 oxidaseP450CYP450
Alternate pathways that make some of the above products include the: a) metabolism of 5(S)-HpETE to 5-oxo-ETE by cytochrome P450 (CYP) enzymes such as CYP1A1, CYP1A2, CYP1B1, and CYP2S1; b) conversion of 5-HETE to 5-oxo-ETE non-enzymatically by heme or other dehydrating agents; c) formation of 5-oxo-15-(S)-hydroxy-ETE through 5-HEDH-based oxidation of 5-(S),15-(S)-dihydroxyicosatetraenoate; d) formation of 5-(S),15(R)-dihydroxy-eicosatetraenoate by the attack of ALOX5 on 15-hydroxyicosatetraenoic acid (15-(S)-HETE); e) formation of 5-oxo-15-(S)-hydroxy-eicosatetreaenoate (5-oxo-15-(S)-hydroxy-ETE) by the arachidonate 15-Lipoxygenase-1-based or arachidonate 15-lipoxygenased-2-based metabolism of 5-oxo-ETE; and f) conversion of 5-(S)-HpETE and 5(R)-HpETE to 5-oxo-ETE by the action of a mouse macrophage 50-60 kilodalton cytosolic protein.

ALOX15

Hydroxycarboxylic acid receptor 2

niacin receptor 1GPR109AHCA 2
It is suggested that this cell's, as well as mouse and other rodent, responses to 5-oxo-ETE are mediated by a receptor closely related to OXER11 viz., the mouse niacin receptor 1, Niacr1.
The mouse ortholog of HCA 2, Niacr1, has been proposed to mediate the ability of 5-oxo-ETE, a member of the 5-HETE family of eicosanoids, to stimulate the production of steroidogenic acute regulatory protein mRNA, Steroidogenic acute regulatory protein, and thereby progesterone in mouse cultured MA-10 Leydig cells.

Eosinophil

eosinophilseosinophil granulocyteEosino
Examples of such cells include neutrophils, eosinophils, B lymphocytes, monocytes, macrophages, mast cells, dendritic cells, and the monocyte-derived foam cells of atherosclerosis tissues.
After maturation, eosinophils circulate in blood and migrate to inflammatory sites in tissues, or to sites of helminth infection in response to chemokines like CCL11 (eotaxin-1), CCL24 (eotaxin-2), CCL5 (RANTES), 5-hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid, and certain leukotrienes like leukotriene B4 (LTB4) and MCP1/4.

Arachidonate 5-lipoxygenase

5-lipoxygenaseALOX55-LOX
5(S)-HETE is a product of the cellular metabolism of the n-6 polyunsaturated fatty acid, arachidonic acid (i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid), by ALOX5 (also termed arachidonate-5-lipoxygenase, 5-lipoxygenase, 5-LO, and 5-LOX).
ALOX5 products, particularly 5-hydroxyeicosatetraenoic acid and 5-oxo-eicosatetraenoic acid, promote the proliferation of these ALOX5 aberrantly expressing tumor cell lines suggesting that ALOX5 acts as a pro-malignancy factor for them and by extension their parent tumors.

Monocyte

monocytesmonocyticmononuclear
Examples of such cells include neutrophils, eosinophils, B lymphocytes, monocytes, macrophages, mast cells, dendritic cells, and the monocyte-derived foam cells of atherosclerosis tissues.
These factors include most particularly chemokines such as monocyte chemotactic protein-1 (CCL2) and monocyte chemotactic protein-3 (CCL7); certain arachidonic acid metabolites such as Leukotriene B4 and members of the 5-Hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid family of OXE1 receptor agonists (e.g., 5-HETE and 5-oxo-ETE); and N-Formylmethionine leucyl-phenylalanine and other N-formylated oligopeptides which are made by bacteria and activate the formyl peptide receptor 1.

15-Hydroxyeicosatetraenoic acid

15-Hydroxyicosatetraenoic acid15(''S'')-hydroperoxyeicosapentaenoic acid15(S)-hydroperoxyeicosatetraenoic acid
Alternate pathways that make some of the above products include the: a) metabolism of 5(S)-HpETE to 5-oxo-ETE by cytochrome P450 (CYP) enzymes such as CYP1A1, CYP1A2, CYP1B1, and CYP2S1; b) conversion of 5-HETE to 5-oxo-ETE non-enzymatically by heme or other dehydrating agents; c) formation of 5-oxo-15-(S)-hydroxy-ETE through 5-HEDH-based oxidation of 5-(S),15-(S)-dihydroxyicosatetraenoate; d) formation of 5-(S),15(R)-dihydroxy-eicosatetraenoate by the attack of ALOX5 on 15-hydroxyicosatetraenoic acid (15-(S)-HETE); e) formation of 5-oxo-15-(S)-hydroxy-eicosatetreaenoate (5-oxo-15-(S)-hydroxy-ETE) by the arachidonate 15-Lipoxygenase-1-based or arachidonate 15-lipoxygenased-2-based metabolism of 5-oxo-ETE; and f) conversion of 5-(S)-HpETE and 5(R)-HpETE to 5-oxo-ETE by the action of a mouse macrophage 50-60 kilodalton cytosolic protein.
5-Oxo-15(S)-hydroxy-ETE is properly a member of the 5-HETE family of agonists which binds to the Oxoeicosanoid receptor 1, a G protein-coupled receptor, to activate its various target cells.

12-Hydroxyeicosatetraenoic acid

12-HETE12(''S'')-hydroxyeicosatetraenoic acid12(S)-HETE

Hormone

hormoneshormonalprohormone
Animal studies and a limited set of human studies suggest that this family of metabolites serve as hormone-like autocrine and paracrine signalling agents that contribute to the up-regulation of acute inflammatory and allergic responses.

Autocrine signaling

autocrineautocrine signallingautocrine loop
Animal studies and a limited set of human studies suggest that this family of metabolites serve as hormone-like autocrine and paracrine signalling agents that contribute to the up-regulation of acute inflammatory and allergic responses.

Paracrine signaling

paracrineparacrine signallinglocal hormones
Animal studies and a limited set of human studies suggest that this family of metabolites serve as hormone-like autocrine and paracrine signalling agents that contribute to the up-regulation of acute inflammatory and allergic responses.

In vitro

in-vitrolaboratoryartificially
In vitro studies suggest that 5(S)-HETE and/or other of its family members may also be active in promoting the growth of certain types of cancers, in simulating bone reabsorption, in signaling for the secretion of aldosterone and progesterone, in triggering parturition, and in contributing to other responses in animals and humans.

Aldosterone

receptors, aldosteroneadrenoglomerulotropin
In vitro studies suggest that 5(S)-HETE and/or other of its family members may also be active in promoting the growth of certain types of cancers, in simulating bone reabsorption, in signaling for the secretion of aldosterone and progesterone, in triggering parturition, and in contributing to other responses in animals and humans.

Progesterone

EndometrinprogestationalProgesterone for prevention of preterm birth
In vitro studies suggest that 5(S)-HETE and/or other of its family members may also be active in promoting the growth of certain types of cancers, in simulating bone reabsorption, in signaling for the secretion of aldosterone and progesterone, in triggering parturition, and in contributing to other responses in animals and humans.