Biosynthesis of A2E, implicated in retinal degradation

Stable Identifier
R-HSA-2466712
Type
Pathway
Species
Homo sapiens
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Summation

Lipofuscin is a yellow-brown pigment grain composed mainly of lipids but also sugars and certain metals. Accumulation of lipofuscin is associated with degenerative diseases such as Alzheimer's disease, Parkinson's disease, chronic obstructive pulmonary disease and retinal macular degeneration.

A prominent component of lipofuscin in retinal pigment epithelial (RPE) cells is the bisretinoid A2E (di-retinoid-pyridinium-ethanolamine), the end-product of the condensation of 2 molecules of all-trans-retinal (atRAL) and phosphatidylethanolamine (PE) in photoreceptor outer disc membranes. Once formed, A2E is phagocytosed, together with outer segments (Kevany & Palczewski 2010), to RPE where it accumulates. There is no evidence as yet to indicate that A2E can be catabolised (Sparrow et al. 2012, Sparrow et al. 2010). A simplified biosynthetic pathway for A2E is described here.

Literature References
PubMed ID Title Journal Year
20134024 Phagocytosis of retinal rod and cone photoreceptors Physiology (Bethesda) 2010
19666736 Phospholipid meets all-trans-retinal: the making of RPE bisretinoids J. Lipid Res. 2010
22209824 The bisretinoids of retinal pigment epithelium Prog Retin Eye Res 2012
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