Lecithin: retinol acyltransferase

Golczak, M, Imanishi, Y, Kuksa, V, Maeda, T, Kubota, R, and Palczewski, K, 2005a. Lecithin Retinol acyltransferase is responsible for amidation of retinylamine, a potent inhibitor of the retinoid cycle. J Biol Chem 280, 42263 12273. 

Retinol (vitamin A) is found in foods of mammalian origin in the form of retinyl ester, or in fruits and vegetables as carotenoids with provitamin A activity, especially P-carotene (provitamin A). In enterocytes, retinol binds to cellular retinol-binding protein type II (CRBPII), which directs the esterification by the enzyme lecithin retinol acyltransferase (LRAT). 

BASF AG CRBPII dba DBN DBU DIBAL-H DMAP DMF DMF-DMA DMPU HMDS HMPA HMPT H-LR LDA LDE LRAT MCPBA MOM NMO NMP PCC PhH = Badische Anilin- Soda Fabrik AG = cellular retinol-binding protein type II r dibenzylideneacetone = 1,5-diazabicyclo[4.3.0]non-5-ene = l,8-diazabicyclo[5.4.0]undec-7-ene = diisobutylaluminium hydride = 4-dimethylaminopyridine = A V-dimethylformamide = A,V-dimethylformamide, dimethylacetal = 1,3 -dimethyl-3,4,5,6-tetrahydro-2( 1H)-pyrimidone = hexamethyldisilazane = hexamethylphosphoramide = hexamethylphosphorous triamide = Hoffmann-La Roche = lithium diisopropylamide = lithium diethylamide = lecithin retinol acyltransferase = m-chloroperbenzoic acid = methoxymethyl = iV-methylmorpholine oxide = l-methyl-2-pyrrolidinone = pyridinium chlorochromate = benzene... 

Within the enterocyte, retinol is bound to cellular retinol binding protein (CRBP 11) and is esterified by lecithin retinol acyltransferase (LRAT), which uses phosphatidylcholine as the fatty acid donor, mainly yielding retinyl palmitate, although small amounts of stearate and oleate are also formed. At unphysiologically high levels of retinol, when CRBP 11 is saturated, acyl coenzyme A (CoA) retinol acyltransferase (ARAT) esterifies the free retinol that accumulates in intracellular membranes. Then the retinyl esters enter the lymphatic circulation and then the bloodstream (in chylomicrons), together with dietary lipid and carotenoids (Norum et al., 1986 Olson, 1986 Blomhoff et al., 1991 Green et al., 1993 Harrison and Hussain, 2001). 

Zolfaghari R and Ross AC (2000) Lecithin retinol acyltransferase from mouse and rat liver. cDNA cloning and liver-specific regulation by dietary vitamin A and retinoic diCid. Journal of Lipid Research 41, 2024-34. 

Fig. 1. The structures of key retinoids and their precursors. Fish convert retinyl esters (e.g. retinyl palmitate (RP)) and carotenoids (e.g. /3-carotene) to retinol in the gut lumen prior to intestinal absorption. Retinyl esters (e.g. RP) stored in the liver are synthesized from retinol by lecithin retinol acyltransferase (LRAT) and acyl CoAiretinol acyltransferase (ARAT). The retinyl esters are mobilized through their conversion to retinol by retinyl ester hydrolase (REH), which is then transported in the circulation to various sites in the body. Retinol is further metabolized within specific tissues to retinal by alcohol dehydrogenases (ADH) or short-chain dehydrogenase/reductase. Retinal is converted to the two major biologically active forms of retinoic acid (RA) (all-trans and 9-cis RA). Retinaldehyde dehydrogenase 2 (Raldh2) synthesizes all-trans RA from all-trans precursors and 9-cis RA form 9-cis precursors.

Shi YQ, Furuyoshi S, Hubacek I, Rando RR (1993) Affinity labeling of lecithin retinol acyltransferase. Biochemistry 32 3077-3080... 

Eppinger TM, Buck J, Hammerling U (1993) Growth control or terminal differentiation endogenous production and differential activities of vitamin A metabolites in HL-60 cqWs. J Exp Med 178 1995-2005 Herr F, Ong DE (1992) Differential interaction of lecithin-retinol acyltransferase with cellular retinoid-binding proteins. Biochemistry 31 6748-6755... 

Figure 3 depicts a model of the functions of multiple proteins and forms of vitamin A that constitute the visual cycle. SRBP delivers atROH to the RPE, possibly through a plasma membrane SRBP receptor. No SRBP receptor has been isolated, however, and molecular characterization remains elusive. As in other tissues, CRBP(I) sequesters atROH and allows its esterification by the 25-kDa endoplasmic reticulum (ER) enzyme lecithin retinol acyltransferase (LRAT). In fact, the amount of CRBP(I) may... 

Figure 4 Model of atRA biogeneration in mammals. REH, retinyl ester hydrolase (e.g., ES4 and ES10) TTR, transthyretin RAR-RXR, the heterodimer of retinoic acid receptors with retinoid X receptors atRCHO, all-frans-relinal atROH, all-frans-retinol CRBP(I), cellular retinol binding protein, type I LRAT, lecithin retinol acyltransferase SRBP, semm retinol binding protein. CRBP(I), CRABP(I), and CRABP(II) have been placed in the same cell for simplicity. This does not necessarily occur in vivo.

Rgure 5 The effect of apo-CRBP(l) on the rates of retinol esterification (lecithin retinol acyltransferase (LRAT)) and retinyl ester hydrolysis (REH). 

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