Reaction: A2PE hydrolyses to A2E
- in pathway: Biosynthesis of A2E, implicated in retinal degradation
The outer segment of photoreceptor cells is shed every 10-14 days to be completely replaced. The shed material is phagocytosed and transferred to the retinal pigment epithelium (RPE). Diretinoid-pyridinium-phosphatidylethanolamine (A2PE) can be hydrolysed to diretinoid-pyridinium-ethanolamine (A2E), a prominent constituent of lipofuscin (the material deposited in retinal tissue which accumulates over time and is implicated in macular degeneration). Evidence suggests this happens before transfer to RPE cells as part of the phagocytosed outer segment. A2E has been detected in outer segments (Ben-Shabat et al. 2002) and an N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPEPLD) activity detected in rat, mouse and human proteins (Okamoto et al. 2004, Ueda et al. 2005, Wang et al. 2006). This activity has been shown to hydrolyse A2PE to A2E in bovine outer segments before phagocytosis and transfer to RPE cells, suggesting A2PE is hydrolysed to A2E in photoreceptor outer segment membranes (Sparrow et al. 2003, Salvador & Giusto 1998).
Reaction - small molecule participants:
PA [cytosol]
A2E [photoreceptor outer segment membrane]
H2O [cytosol]
A2PE [photoreceptor outer segment membrane]
Reactome.org reaction link: R-HSA-2466831
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Reaction input - small molecules:
water
N-retinylidene-N-retinylphosphatidylethanolamine
Reaction output - small molecules:
phosphatidate(2-)
N-retinylidene-N-retinylethanolamine
Reactome.org link: R-HSA-2466831