Meta-Biol

• Pathways

The esterification of alcohols with fatty acids is the favoured mechanism to form esterified forms of sterols, di- and triacylglycerols, and retinoids for storage. In the RPE and Muller cells of the eye, formation of retinyl esters is an essential step in the enzymatic regeneration of the visual chromophore 11-cis-retinal (11cRAL). Acyl-CoA wax alcohol acyltransferase 2 (AWAT2, aka Multifunctional O-acyltransferase, MFAT) (Yen et al. 2005) is an ER-membrane protein with a broad substrate specificity that can also esterify 11-cis retinol (11cROL) (Kaylor et al. 2014). The most common fatty acid is palmitate, forming retinyl palmitate (11cRPALM). Retinyl esters form into lipid droplets called retinosomes. In the previous step, retinol isomerase activity produces a mixture of retinol isomers (9-cis, 11-cis, 13-cis and all-trans-retinol) of which 11cROL only constitutes around 1% of the mixture. AWAT2’s preferential activity towards 11cROL has been proposed to be due to an allosteric modulation of AWAT2 by either bound (to RLBP1) or free 11cis-retinyl esters such as 11cRPALM. 11cRPALM impedes the acyl transfer onto 9-cis, 13-cis and all-trans retinols by making allosterically-induced changes in the active site of AWAT2 (Arne et al. 2017).