Levuglandin Explained

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.^[1] They are nonclassic eicosanoids. One species, levuglandin E₂, (LGE₂), forms neurotoxic adducts with amyloid beta.^{[2] [3]} 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.^{[4] [5]} Prof. Robert Salomon at Case Western Reserve University discovered that a novel alternative rearrangement also occurs that producing two γ-ketoaldehydes^[6] and named them levuglandins LGD2 and LGE2 as they are derivatives of levulinaldehyde with prostanoid side chains.

References

1. Salomon RG . Isolevuglandins, oxidatively truncated phospholipids, and atherosclerosis . Ann. N. Y. Acad. Sci. . 1043 . 327–42 . 2005 . 1 . 16037255 . 10.1196/annals.1333.040. 2005NYASA1043..327S . 12782911 .
2. 10.1111/j.1471-4159.2005.03586.x. PGH2-derived levuglandin adducts increase the neurotoxicity of amyloid beta1-42. 2006. Boutaud. Olivier. Montine. Thomas J.. Chang. Lei. Klein. William L.. Oates. John A.. Journal of Neurochemistry. 96. 4. 917–923. 16412101. 1621054.
3. 10.1021/bi990470+. 10413514. 1999. Boutaud. O.. Brame. C. J.. Salomon. R. G.. Roberts Lj. 2nd. Oates. J. A.. Characterization of the lysyl adducts formed from prostaglandin H2 via the levuglandin pathway. Biochemistry. 38. 29. 9389–96.
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 . 10.1073/pnas.70.3.899. 433384 . 4514999. 1973PNAS...70..899H . free .
5. Nugteren D.H., Hazelhof E. . 1973 . Isolation and properties of intermediates in prostaglandin biosynthesis . Biochim. Biophys. Acta . 326 . 3. 448–461 . 10.1016/0005-2760(73)90145-8. 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 . 10.1021/ja00332a049.