Levuglandin

Levuglandin D2
Names
IUPAC name
(5Z,8R,9R,10E,12S)-9-acetyl-8-formyl-12- hydroxyheptadeca-5,10-dienoic acid
Identifiers
3D model (JSmol)
ChemSpider
KEGG
UNII
  • InChI=1S/C20H32O5/c1-3-4-7-11-18(23)13-14-19(16(2)22)17(15-21)10-8-5-6-9-12-20(24)25/h5,8,13-15,17-19,23H,3-4,6-7,9-12H2,1-2H3,(H,24,25)/b8-5-,14-13+/t17-,18-,19-/m0/s1 X markN
    Key: MLLWPVVMXGUOHD-QNUMDXCLSA-N X markN
  • CCCCC[C@@H](/C=C/[C@H]([C@@H](C/C=C\CCCC(=O)O)C=O)C(=O)C)O
Properties
C20H32O5
Molar mass 352.465 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Levuglandin E2
Names
IUPAC name
(5Z,8R,9R,10E,12S)-8-acetyl-9-formyl-12- hydroxyheptadeca-5,10-dienoic acid
Other names
LGE2
Identifiers
3D model (JSmol)
ChemSpider
KEGG
  • InChI=1S/C20H32O5/c1-3-4-7-10-18(23)14-13-17(15-21)19(16(2)22)11-8-5-6-9-12-20(24)25/h5,8,13-15,17-19,23H,3-4,6-7,9-12H2,1-2H3,(H,24,25)/b8-5-,14-13+/t17-,18-,19-/m0/s1
    Key: WJWAORNTZNRHBP-QNUMDXCLSA-N
  • CCCCC[C@@H](/C=C/[C@@H](C=O)[C@@H](C/C=C\CCCC(=O)O)C(=O)C)O
Properties
C20H32O5
Molar mass 352.465 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Levuglandins are reactive aldehydes formed by the spontaneous rearrangement of prostaglandin H (PGH). Enantiomerically pure levuglandin (LG) E2 can also be formed through the cyclooxygenase (COX) pathway by a rearrangement of the prostaglandin (PG) endoperoxide PGH 2. They are nonclassic eicosanoids. One species, levuglandin E2, (LGE2), forms neurotoxic adducts with amyloid beta. Levuglandins and isolevuglandins can damage proteins by covalent adduction, thereby interfering with their normal functions. These lipid-derived protein modifications may serve as dosimeters of oxidative injury. Elevated plasma levels of isoLG-protein epitopes are associated with atherosclerosis but are independent of total cholesterol, a classical risk factor.

History

Though spontaneous rearrangements of PGH2 are known to generate prostaglandins (PG) PGD2 and PGE2. Prof. Robert Salomon at Case Western Reserve University discovered that a novel alternative rearrangement also occurs that producing two γ-ketoaldehydes and named them levuglandins LGD2 and LGE2 as they are derivatives of levulinaldehyde with prostanoid side chains.

References

  1. ↑ Salomon RG (2005). "Isolevuglandins, oxidatively truncated phospholipids, and atherosclerosis". Ann. N. Y. Acad. Sci. 1043 (1): 327–42. Bibcode:2005NYASA1043..327S. doi:10.1196/annals.1333.040. PMID 16037255. S2CID 12782911.
  2. ↑ Boutaud, Olivier; Montine, Thomas J.; Chang, Lei; Klein, William L.; Oates, John A. (2006). "PGH2-derived levuglandin adducts increase the neurotoxicity of amyloid beta1-42". Journal of Neurochemistry. 96 (4): 917–923. doi:10.1111/j.1471-4159.2005.03586.x. PMC 1621054. PMID 16412101.
  3. ↑ Boutaud, O.; Brame, C. J.; Salomon, R. G.; Roberts Lj, 2nd; Oates, J. A. (1999). "Characterization of the lysyl adducts formed from prostaglandin H2 via the levuglandin pathway". Biochemistry. 38 (29): 9389–96. doi:10.1021/bi990470+. PMID 10413514.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  4. ↑ Hamberg M., Samuelsson B. (1973). "Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis". Proc. Natl. Acad. Sci. U.S.A. 70 (3): 899–903. Bibcode:1973PNAS...70..899H. doi:10.1073/pnas.70.3.899. PMC 433384. PMID 4514999.
  5. ↑ Nugteren D.H., Hazelhof E. (1973). "Isolation and properties of intermediates in prostaglandin biosynthesis". Biochim. Biophys. Acta. 326 (3): 448–461. doi:10.1016/0005-2760(73)90145-8. PMID 4776443.
  6. ↑ Salomon R.G.; Miller D.B.; Zagorski M.G.; Coughlin D.J. (1984). "Prostaglandin endoperoxides. 14. Solvent-induced fragmentation of prostaglandin endoperoxides. New aldehyde products from PGH2 and a novel intramolecular 1*2-hydride shift during endoperoxide fragmentation in aqueous solution". J. Am. Chem. Soc. 106 (20): 6049–6060. doi:10.1021/ja00332a049.