Reactome | AWAT2 transfers PALM to 11cROL forming 11cRPALM

AWAT2 transfers PALM to 11cROL forming 11cRPALM

Stable Identifier

R-HSA-2465919

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, endoplasmic reticulum membrane

ReviewStatus

5/5

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AWAT2 transfers PALM to 11cROL forming 11cRPALM

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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).

Literature References

PubMed ID	Title	Journal	Year
24799687	Identification of the 11-cis-specific retinyl-ester synthase in retinal Müller cells as multifunctional O-acyltransferase (MFAT) Travis, GH, Yong, J, Cook, JD, Kaylor, JJ, Makshanoff, J, Bischoff, N	Proc. Natl. Acad. Sci. U.S.A.	2014
16106050	A human skin multifunctional O-acyltransferase that catalyzes the synthesis of acylglycerols, waxes, and retinyl esters Brown, CH, Farese, RV, Monetti, M, Yen, CL	J. Lipid Res.	2005
28096191	Allosteric modulation of the substrate specificity of acyl-CoA wax alcohol acyltransferase 2 (AWAT2) Hughes, T, Huynh, KW, Golczak, M, Chelstowska, S, Silvaroli, JA, Widjaja-Adhi, MA, Moiseenkova-Bell, VY, Arne, JM	J. Lipid Res.	2017