15-Hydroxyeicosatetraenoic acid

15-Hydroxyeicosatetraenoic acid
Names
Preferred IUPAC name
(5Z,8Z,11Z,13E,15S)-15-Hydroxyicosa-5,8,11,13-tetraenoic acid
Other names
15-HETE, 15(S)-HETE, 15(S)-HETE
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.214.805 Edit this at Wikidata
UNII
  • InChI=1S/C20H32O3/c1-2-3-13-16-19(21)17-14-11-9-7-5-4-6-8-10-12-15-18-20(22)23/h4-5,8-11,14,17,19,21H,2-3,6-7,12-13,15-16,18H2,1H3,(H,22,23)/b5-4-,10-8-,11-9-,17-14+/t19-/m0/s1
    Key: JSFATNQSLKRBCI-VAEKSGALSA-N
  • CCCCC[C@@H](/C=C/C=C\C/C=C\C/C=C\CCCC(=O)O)O
Properties
C20H32O3
Molar mass 320.473 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

15-Hydroxyeicosatetraenoic acid (also termed 15-HETE, 15(S)-HETE, and 15S-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid. Various cell types metabolize arachidonic acid to 15(S)-hydroperoxyeicosatetraenoic acid (15(S)-HpETE). This initial hydroperoxide product is extremely short-lived in cells: if not otherwise metabolized, it is rapidly reduced to 15(S)-HETE. Both of these metabolites, depending on the cell type which forms them, can be further metabolized to 15-oxo-eicosatetraenoic acid (15-oxo-ETE), 5(S),15(S)-dihydroxy-eicosatetraenoic acid (5(S),15(S)-diHETE), 5-oxo-15(S)-hydroxyeicosatetraenoic acid (5-oxo-15(S)-HETE), a subset of specialized pro-resolving mediators viz., the lipoxins, a class of pro-inflammatory mediators, the eoxins, and other products that have less well-defined activities and functions. Thus, 15(S)-HETE and 15(S)-HpETE, in addition to having intrinsic biological activities, are key precursors to numerous biologically active derivatives.[1][2]

Some cell types (e.g. platelets) metabolize arachidonic acid to the stereoisomer of 15(S)-HpETE, 15(R)-HpETE. Both stereoisomers may also be formed as result of the metabolism of arachidonic acid by cellular microsomes or as a result of arachidonic acid auto-oxidation. Similar to 15(S)-HpETEs, 15(R)-HpETE may be rapidly reduced to 15(R)-HETE. These R,S stereoisomers differ only in having their hydroxy residue in opposite orientations. While the two R stereoisomers are sometimes referred to as 15-HpETE and 15-HETE, proper usage should identify them as R stereoisomers. 15(R)-HpETE and 15(R)-HETE lack some of the activity attributed to their S stereoisomers but can be further metabolized to bioactive products viz., the 15(R) class of lipoxins (also termed epi-lipoxins).[3]

15(S)-HETE, 15(S)-HpETE, and many of their derivative metabolites are thought to have physiologically important functions. They appear to act as hormone-like autocrine and paracrine signaling agents that are involved in regulating inflammatory and perhaps other responses.[1][2][4] Clinically, drugs that are stable analogs, and therefore mimic the anti-inflammatory actions of the lipoxins and drugs that block the production or actions of the pro-inflammatory eoxins may prove useful for treating acute and chronic inflammatory disorders.[5]

  1. ^ a b Moreno, J. J. (2009). "New aspects of the role of hydroxyeicosatetraenoic acids in cell growth and cancer development". Biochemical Pharmacology. 77 (1): 1–10. doi:10.1016/j.bcp.2008.07.033. PMID 18761324.
  2. ^ a b Schneider, C; Pozzi, A (2011). "Cyclooxygenases and lipoxygenases in cancer". Cancer and Metastasis Reviews. 30 (3–4): 277–294. doi:10.1007/s10555-011-9310-3. PMC 3798028. PMID 22002716.
  3. ^ Buckley, C. D.; Gilroy, D. W.; Serhan, C. N. (2014). "Proresolving lipid mediators and mechanisms in the resolution of acute inflammation". Immunity. 40 (3): 315–327. doi:10.1016/j.immuni.2014.02.009. PMC 4004957. PMID 24656045.
  4. ^ Zhu, D; Ran, Y (2012). "Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension". The Journal of Physiological Sciences. 62 (3): 163–172. doi:10.1007/s12576-012-0196-9. PMC 10717549. PMID 22331435. S2CID 2723454.
  5. ^ Leeper KV (1993). "Diagnosis and treatment of pulmonary infections in adult respiratory distress syndrome". New Horizons (Baltimore, Md.). 1 (4): 550–562. PMID 8087575.