Oxidation of A2E results in the formation of highly reactive aldehydes and ketones.
It has been reported that the photo-oxidation of A2E, a component of human retinal lipofuscin, leads to products that are toxic to cells via dark reactions. Because these compounds have been implicated in the development of various maculopathies such as age-related macular degeneration (AMD), it is important to determine the structures of those deleterious compounds. Both the photo-oxidation and auto-oxidation of A2E lead to the same complex mixture of products, some of which have lower molecular weights than the staring material. Because A2E is homologous to beta-carotene, it was hypothesized that its oxidation would lead to products analogous to those found in oxidized beta-carotene, namely, a series of cleavage products along the acyclic chain with the concomitant formation of aldehydes. This was found to be the case based upon 1) the formation of all of the aldehydes predicted from the oxidation of beta-carotene, 2) the loss of 28 amu (carbonyl moiety) from the molecular ion, 3) the facile reaction of the aldehydes with nitrophenylhydrazines to form nitrophenylhydrazones and 4) the subsequent MS/MS cleavage of those derivatives at the N-N bond. If formed in vivo, these aldehydes would have toxic effects on any cell. Finally, the similarity in product mixtures from both the photo-oxidation and auto-oxidation strongly suggests that the intermolecular photo-oxidation of A2E results primarily from a radical process without the involvement of singlet oxygen. Any formation of singlet oxygen most likely arises from sensitization by the aldehyde oxidation products, as this process is well known for aldehydes, in general, and retinal, specifically.
Wang
Zhen
Z
Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL, USA.
Keller
Lanea M M
LM
Dillon
James
J
Gaillard
Elizabeth R
ER
D000447:Aldehydes / Q000378:metabolism; D006801:Humans; D007659:Ketones / Q000378:metabolism; D008027:Light; D008062:Lipofuscin / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000528:radiation effects; D011726:Pyridinium Compounds / Q000737:chemistry / Q000378:metabolism*; D012176:Retinoids / Q000737:chemistry / Q000378:metabolism*
C112040:A2-E (N-retinylidene-N-retinylethanolamine); D000447:Aldehydes; D007659:Ketones; D008062:Lipofuscin; D011726:Pyridinium Compounds; D012176:Retinoids