Levuglandins are reactive
aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
s formed by the spontaneous rearrangement of
prostaglandin H (PGH). Enantiomerically pure levuglandin (LG) E
2 can also be formed through the cyclooxygenase (COX) pathway by a rearrangement of the prostaglandin (PG) endoperoxide PGH
2.
They are
nonclassic eicosanoid Nonclassic eicosanoids are biologically active signaling molecules made by oxygenation of twenty-carbon fatty acids other than the classic eicosanoids.
Terminology
:
"Eicosanoid" is the collective
term for oxygenated derivatives of three differe ...
s. One species, levuglandin E
2, (LGE
2), forms neurotoxic
adduct
An adduct (from the Latin ''adductus'', "drawn toward" alternatively, a contraction of "addition product") is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all co ...
s with
amyloid beta
Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...
.
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
[{{cite journal , author1=Salomon R.G. , author2=Miller D.B. , author3=Zagorski M.G. , author4=Coughlin D.J. , year = 1984 , title = 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 , journal = J. Am. Chem. Soc. , volume = 106 , issue = 20, pages = 6049–6060 , doi=10.1021/ja00332a049] and named them levuglandins LGD2 and LGE2 as they are derivatives of levulinaldehyde with prostanoid side chains.
References
Eicosanoids