A lecithin: Retinol acyltransferase activity in human and rat liver

MacDonald, Paul N.; Ong, David E.

doi:10.1016/s0006-291x(88)80818-0

Cited by 139 publications

(113 citation statements)

References 18 publications

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“…In contrast, while using radiation inactivation analysis on intact microsomal membranes from rat liver the activity of LRAT yielded a target size averaging 52-56 kDa (21). In addition to RPE and liver, LRAT activity has also been reported in several other tissues such as, testis, intestine, and pancreas (11,22,23), suggesting a role in essential biological processes. Because of the physiological relevance of LRAT, particularly in the metabolism and storage of vitamin A, its molecular characterization is of vital importance.…”

Section: High Performance Liquid Chromatography Analysis Of the Reactmentioning

confidence: 99%

Molecular and Biochemical Characterization of Lecithin Retinol Acyltransferase

Ruíz¹,

Winston²,

Lim³

et al. 1999

Journal of Biological Chemistry

235

300

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The enzyme responsible for conversion of all-transretinol into retinyl esters, the lecithin retinol acyltransferase (LRAT) has been characterized at the molecular level. The cDNA coding for this protein was cloned and its amino acid sequence deduced. LRAT is composed of a polypeptide of 230 amino acid residues with a calculated mass of 25.3 kDa. Tissue distribution analysis by Northern blot showed expression of a 5.0-kilobase transcript in the human retinal pigment epithelium as well as in other tissues that are known for their high LRAT activity and vitamin A processing. Affinity labeling experiments using specific compounds with high affinity for LRAT and monospecific polyclonal antibodies raised in rabbits against two peptide sequences for LRAT confirmed the molecular mass of LRAT as a 25-kDa protein. Vitamin A (retinol) is the substrate for the biosynthesis of several functional retinoids (retinol derivatives) which are essential for important biological processes such as, vision, reproduction, and development (for review, see Ref. 1). The small intestinal epithelium is the first site of interaction and processing of retinol after absorption from the diet. Within this epithelium, the final processing step involves the esterification of retinol with long chain fatty acids, primarily palmitic, and incorporation of the retinyl esters into the hydrophobic core of chylomicrons which are secreted into the lymph and ultimately enter the blood via the thoracic and other lymphatic ducts (2). Chylomicron remnants are taken up by the liver and the retinyl esters are stored until needed. Following de-esterification by the liver, retinol is complexed with a 21-kDa retinol-binding protein (RBP) 1 and secreted into the circulation as a complex with transthyretin whereby it is distributed to other tissues (3). Both proteins are thought to transport and protect retinol from oxidation and/or isomerization during the distribution process. In the eye, and more specifically in the retinal pigment epithelium (RPE), this retinol complex interacts with the basal membrane of RPE cells probably via an RBP receptor (4, 5), where retinol is delivered into the cytoplasm to initiate a unique and highly specialized process for the RPE, the visual cycle (for review, see Refs. 6 -8). During this important process, the retinol bound to a cellular retinol-binding protein (CRBP), is trans-esterified by an enzyme named lecithin retinol acyltransferase (LRAT) (9 -11) that transfers an acyl group from lecithin to retinol to generate all-trans-retinyl esters. All-trans-retinyl esters generated by the activity of LRAT are not only presumptive storage forms of vitamin A, but they are also substrates for an isomerohydrolase which transforms the esters into an intermediate 11-cis-retinol (12, 13). Due to a membrane-associated alcohol dehydrogenase (14, 15), 11-cis-retinol is then oxidized and converted into 11-cis-retinaldehyde which is the chromophore for rhodopsin and the cone photopigments. In the RPE, the esterification process of retinol by LRA...

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Section: High Performance Liquid Chromatography Analysis Of the Reactmentioning

confidence: 99%

Molecular and Biochemical Characterization of Lecithin Retinol Acyltransferase

Ruíz¹,

Winston²,

Lim³

et al. 1999

Journal of Biological Chemistry

235

300

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“…In CRBP-II-KO mice, investigators found that CRBP-II plays an important (albeit not essential) role in the absorption of vitamin A from the intestine (47). Some of the free retinol in the enterocytes remains associated with CRBP, but much of the retinol is usually esterified by lecithin:retinol acyltransferases (LRATs) and stored within the cell (116). The recent characterization of the LRAT-KO mouse [in which no detectable tissue retinyl esters were found (9)] has largely resolved the question of whether enzymes such as ARAT are physiologically involved in retinol esterification in the intestine.…”

Section: Vitamin Ementioning

confidence: 99%

Intestinal lipid absorption

Iqbal¹,

Hussain²

2009

American Journal of Physiology-Endocrinology and Metabolism

648

484

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Our knowledge of the uptake and transport of dietary fat and fat-soluble vitamins has advanced considerably. Researchers have identified several new mechanisms by which lipids are taken up by enterocytes and packaged as chylomicrons for export into the lymphatic system or clarified the actions of mechanisms previously known to participate in these processes. Fatty acids are taken up by enterocytes involving protein-mediated as well as proteinindependent processes. Net cholesterol uptake depends on the competing activities of NPC1L1, ABCG5, and ABCG8 present in the apical membrane. We have considerably more detailed information about the uptake of products of lipid hydrolysis, the active transport systems by which they reach the endoplasmic reticulum, the mechanisms by which they are resynthesized into neutral lipids and utilized within the endoplasmic reticulum to form lipoproteins, and the mechanisms by which lipoproteins are secreted from the basolateral side of the enterocyte. apoB and MTP are known to be central to the efficient assembly and secretion of lipoproteins. In recent studies, investigators found that cholesterol, phospholipids, and vitamin E can also be secreted from enterocytes as components of high-density apoB-free/apoAI-containing lipoproteins. Several of these advances will probably be investigated further for their potential as targets for the development of drugs that can suppress cholesterol absorption, thereby reducing the risk of hypercholesterolemia and cardiovascular disease.intestine; dietary fat; triacylglycerol; cholesterol; phospholipids; fat-soluble vitamins; microsomal triglyceride transfer protein DIETARY FATS CONSIST OF A WIDE ARRAY of polar and nonpolar lipids (32, 33). Triacylglycerol (TAG) is the dominant fat in the diet, contributing 90 -95% of the total energy derived from dietary fat. Dietary fats also include phospholipids (PLs), sterols (e.g., cholesterol), and many other lipids (e.g., fatsoluble vitamins). The predominant PL in the intestinal lumen is phosphatidylcholine (PC), which is derived mostly from bile (10 -20 g/day in humans) but also from the diet (ϳ1-2 g/day). The predominant dietary sterols are cholesterol (mostly of animal origin) and ␤-sitosterol (the major plant sterol). Although ␤-sitosterol accounts for 25% of dietary sterols, it is not absorbed by humans under physiological conditions.Researchers have been investigating the various steps involved in lipid digestion, absorption, and metabolism to identify factors that could serve as targets for the development of drugs capable of reducing the risk of lipid-associated disorders, including dyslipidemias and cardiovascular disease. In so doing, they have explored key aspects of lipid digestion hydrolysis, emulsification, and micelle formation. They have also explored key issues of absorption, e.g., the uptake of the products of lipid hydrolysis by enterocytes (the epithelial cells lining the walls of the intestinal lumen) and their transport to intracellular compartments, where fatty acids and sterols are...

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“…including the liver, lung, pancreas, intestine, testis, and the retinal pigmented epithelium (RPE) (1)(2)(3)(4)(5). LRAT activity in the RPE has been studied for more than 60 years (6), but the enzyme was only recently identified on the molecular level as a 25-kDa integral membrane protein (7).…”

mentioning

confidence: 99%

Lecithin-retinol Acyltransferase Is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver

Batten

Imanishi

Maeda

et al. 2004

Journal of Biological Chemistry

324

380

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Lecithin-retinol acyltransferase (LRAT), an enzyme present mainly in the retinal pigmented epithelial cells and liver, converts all-trans-retinol into all-trans-retinyl esters. In the retinal pigmented epithelium, LRAT plays a key role in the retinoid cycle, a two-cell recycling system that replenishes the 11-cis-retinal chromophore of rhodopsin and cone pigments. We disrupted mouse Lrat gene expression by targeted recombination and generated a homozygous Lrat knock-out (Lrat؊/؊) mouse. Despite the expression of LRAT in multiple tissues, the Lrat؊/؊ mouse develops normally. The histological analysis and electron microscopy of the retina for 6 -8-week-old Lrat؊/؊ mice revealed that the rod outer segments are ϳ35% shorter than those of Lrat؉/؉ mice, whereas other neuronal layers appear normal. Lrat؊/؊ mice have trace levels of all-trans-retinyl esters in the liver, lung, eye, and blood, whereas the circulating all-trans-retinol is reduced only slightly. Scotopic and photopic electroretinograms as well as pupillary constriction analyses revealed that rod and cone visual functions are severely attenuated at an early age. We conclude that Lrat؊/؊ mice may serve as an animal model with early onset severe retinal dystrophy and severe retinyl ester deprivation.Lecithin-retinol acyltransferase (LRAT) 1 converts all-transretinol (vitamin A) to all-trans-retinyl esters in several tissues, including the liver, lung, pancreas, intestine, testis, and the retinal pigmented epithelium (RPE) (1-5). LRAT activity in the RPE has been studied for more than 60 years (6), but the enzyme was only recently identified on the molecular level as a 25-kDa integral membrane protein (7). All-trans-retinyl esters are intermediate compounds in a metabolic pathway ("visual cycle" or "retinoid cycle") that recycles 11-cis-retinal, the chromophore of rhodopsin and cone pigments (for review, see Refs. 8 -10). In this cycle, all-trans-retinal dissociates from rhodopsin and cone pigments after photobleaching. In the photoreceptors, all-trans-retinal is reduced to all-trans-retinol and subsequently exported to the adjacent RPE. In the RPE, alltrans-retinol is esterified by LRAT and stored. All-trans-retinyl esters have been suggested to be the substrate for a putative isomerohydrolase in the RPE (11) and for a retinyl ester hydrolase that produces all-trans-retinol, a substrate for the putative isomerase (for review, see Ref. 12). Ultimately, 11-cisretinol is produced, oxidized to 11-cis-retinal, and exported to the photoreceptors. In the rod and cone photoreceptor outer segments, 11-cis-retinal recombines with opsins to form rhodopsin and cone pigments (for review, see Ref. 8).Human LRAT cDNA was cloned from a retinal-RPE cDNA library (7) and rodent Lrat cDNA from liver and other tissues (13-15). Lrat mRNA was shown to be a 5.0-kb species expressed in the RPE, and the multiple transcripts based on differential polyadenylation were detected in several other tissues known for the highest LRAT activity (13). The human LRAT polypeptide consisted of 230 ...

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A lecithin: Retinol acyltransferase activity in human and rat liver

Cited by 139 publications

References 18 publications

Molecular and Biochemical Characterization of Lecithin Retinol Acyltransferase

Molecular and Biochemical Characterization of Lecithin Retinol Acyltransferase

Intestinal lipid absorption

Lecithin-retinol Acyltransferase Is Essential for Accumulation of All-trans-Retinyl Esters in the Eye and in the Liver

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