Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids

Abstract

Vitamin A is an essential nutrient for humans and is converted to the visual chromophore, 11-cis-retinal, and to the hormone, retinoic acid. Vitamin A in animal-derived foods is found as long chain acyl esters of retinol and these are digested to free fatty acids and retinol before uptake by the intestinal mucosal cell. The retinol is then reesterified to retinyl esters for incorporation into chlylomicrons and absorbed via the lymphatics or effluxed into the portal circulation facilitated by the lipid transporter, ABCA1. Provitamin A carotenoids such as β-carotene are found in plant-derived foods. These and other carotenoids are transported into the mucosal cell by scavenger receptor class B type I (SR-BI). Provitamin A carotenoids are partly converted to retinol by oxygenase and reductase enzymes and the retinol so produced is available for absorption via the two pathways described above. The efficiency of vitamin A and carotenoid intestinal absorption is determined by the regulation of a number of proteins involved in the process. Polymorphisms in genes for these proteins lead to individual variability in the metabolism and transport of vitamin A and carotenoids. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism.

Fig. 1

Products of the central and eccentric cleavages of β-carotene. Oxidative cleavage of β-carotene at the 15,15′ double bond is catalyzed by the enzyme β-carotene 15,15′-oxygenase 1 (BCO1) and leads to the generation of two molecules of retinal. Cleavage at other double bonds leads to the formation of β-apocarotenals and β-apocarotenones. For example the cleavage at the 9′,10′ double bond is catalyzed by β-carotene 9′10′-oxygenase 2 (BCO2) and leads to the formation of β-apo-10′-carotenal and β-ionone (BI). Eccentric cleavage at other double bonds may occur nonenzymatically or may be enzyme catalyzed. Presumably the β-apocarotenals can be oxidized to the corresponding β-apocarotenoic acids by non-specific aldehyde dehydrogenases but this has not been clearly demonstrated. The mechanism of possible chain shortening of β-apocarotenals and β-apocarotenoic acids (dotted lines) is also not known.

Fig. 2

Overview of intestinal absorption of dietary vitamin A and carotenoids. Dietary retinyl esters (RE) are hydrolyzed in the lumen by the pancreatic enzymes, pancreatic triglyceride lipase (PTL) and pancreatic lipase-related protein 2 (PLRP2), and the intestinal brush border enzyme, phospholipase B (PLB). Unesterified retinol (ROH) is taken up by the enterocyte, perhaps via passive diffusion. Once in the cell, retinol is complexed with cellular retinol-binding protein type 2 (CRBP2) and the complex serves as a substrate for re-esterification of the retinol by the enzyme lecithin:retinol acyltransferase (LRAT). The RE are then incorporated into chylomicrons, intestinal lipoproteins containing other dietary lipids (such as triglyceride, phospholipids, cholesterol, and cholesteryl esters) and apolipoprotein B (apoB). The incorporation of some of these lipids is dependent on the activity of microsomal triglyceride transfer protein. Dietary provitamin A carotenoids (e.g. β-carotene) and other carotenoids are taken up by intestinal cells perhaps by facilitated processes involving scavenger receptor class B type I (SR-BI). β-Carotene is partially converted to retinol by β-carotene oxygenase 1 (BCO1) and retinal reductase. The retinol so formed is then metabolized like that originating from preformed vitamin A. The intact carotenoids are incorporated into nascent chylomicrons. Chylomicrons containing newly absorbed retinyl esters and carotenoids (RE, car) are then secreted into the lymph. Unesterified retinol is also absorbed into the portal circulation and its efflux from the basolateral cell membrane is facilitated by the lipid transporter, ABCA1.