Vitamin A Uptake and Metabolism

Vitamin A can be obtained either as the provitamin (mostly p-carotenes) from plant sources or as its fatty acid ester (RE = retinyl ester) from animal sources. The lipophilic retinyl esters (RE) are hydrolyzed by a pancreatic lipase (cholesterol esterase) during lipid digestion (A). Retinol (R) is absorbed into the mucosa cells where it is reesterified in one of two ways: retinol supplied at physiological levels is first bound to a specific cellular retinol-binding protein (CRBP II). If supplied in very large amounts it can also be esterified directly. The esters are integrated into chylomicrons (CM) and carried to the blood via lymphatic fluid. Receptor-mediated hepatic uptake occurs after the chylomicrons have been converted to remnants (REM). After hydrolysis of the retinyl esters, retinol can either be bound to CRBP in the parenchymal cells, or transported to the hepatic perisinu-soidal cells. There, it is reesterified and constitutes the body's most important vitamin A pool (50-80%). Hepatic vitamin A release occurs through bonding of retinol to retinol-binding protein (RBP). Due to its low molecular weight (21 000), the RBP-retinol complex would be quickly lost to renal excretion. Its coupling to trans-thyretin (TTR) prevents such loss during renal filtration (RBP-TTR-retinol complex).

Cellular uptake (B) of vitamin A can occur in two ways. After binding to a receptor, retinol can be released from the RBP-TTR-retinol complex formed in the liver. The remaining RBP is degraded renally. After absorption, there is either intracellular binding to CRBP, oxidation to retinoic acid, or reesterification through either acyl-CoA-retinol acyl-

transferase (ARAT) or retinol acyltrans-ferase (LRAT). The resulting retinyl esters constitute an intracellular pool that can be accessed through hydrolysis (retinyl ester hydrolases - REH). Retinyl esters can also be derived directly from lipid metabolism: during degradation of chylomicrons to remnants, lipoprotein lipase (LPL) releases not only free fatty acids but also retinyl esters, all of which are absorbed by cells, enabling vitamin A supply to target cells independently of the controlled hepatic release of the RBP-TTR-retinol complex.

An additional possibility is direct oral supply of retinoic acid. In the blood, the latter is bound to albumin and attaches to a specific cellular retinoic acid-binding protein (CRABP) inside cells. Retin-oic acid can pass the cell membrane and bind to a specific nuclear receptor, more than 30 variants of which have been described to date. The nuclear retinoid receptors act as transcription factors by binding to specific DNA sequences. They control the expression of many factors, particularly factors regulating growth and tissue and cell differentiation. Among them are growth hormone receptors, oncogenes, interleukins, cytokines, and cell-cell interaction factors.

A. Absorption

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Fatty acids

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