Biosynthesis, Absorption, Metabolism and Transport of Retinoids

Abstract

All retinoids (vitamin A and its analogs) in the body originate in the diet either as preformed vitamin A, usually from animal food sources, or as provitamin A carotenoids, usually from plant food sources or as supplements or additives to processed foods. Both preformed vitamin A and provitamin A undergo metabolism within the intestine (BLANER and OLSON 1994), including a series of metabolic conversions, extracellularly in the lumen of the intestine and intracellularly in the intestinal mucosa, which result in the preponderance of the dietary vitamin A being converted to retinol (vitamin A alcohol). The retinol, along with other dietary lipids in the intestinal mucosa, is packaged as retinyl ester in nascent chylomicrons. The chylomicrons are secreted into the lymphatic system, and approximately 75% of chylomicron retinoid is eventually taken up as part of the chylomicron remnants by the liver, where the majority of the body's retinoid reserves are stored. Some retinoid is delivered to extrahepatic tissues where this retinoid is either stored as retinyl ester, released back into the circulation for delivery to the liver and other tissues, metabolized to active retinoid forms such as retinoic acid or metabolized to catabolic forms destined for excretion from the body.The predominant retinoid present in the fasting circulation is the retinoic acid precursor, retinol. Since retinol is not soluble in aqueous environments, all circulating retinol is bound to retinol-binding protein (RBP). Other retinoids are also present in blood, albeit at much lower concentrations than retinol. Both all-trans-and 13-cis-retinoic acid can be found in fasting plasma of both animals and humans. Some retinyl ester is present as a component of lipoproteins, especially in very low density lipoprotein (VLDL) and low density lipoprotein (LDL). Glucuronides of both retinol and retinoic acid can be found in the circulation along with low levels of retro-metabolites of retinol.This chapter focuses primarily on recent advances in our understanding of the uptake and metabolism of dietary retinoid and provitamin A carotenoids, retinoid storage and metabolism in the liver and the delivery of retinoid to target tissues. Thus this review is concerned primarily with the metabolism and transport of the precursor retinol and its storage form, retinyl ester. Later chapters review the formation and catabolism of active retinoid forms such as retinoic acid and retro-retinoids from retinol.

Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background

“…In hepatocytes, newly synthesized RBP4 associates with retinol and transthyretin (TTR) in the endoplasmic reticulum and is then secreted into the blood. [1][2][3][4][5] Thus, RBP4 is essential for the mobilization of retinol from liver stores. Binding to TTR (a tetramer of MW 55 000) prevents renal filtration of RBP4 (MW 21 000).…”

Reduced Lecithin

“…ROL (vitamin A) can be metabolized into a variety of structurally related compounds, many of which have independent biological activity in various cell types (20,21). For example, the esterification of ROL to retinyl esters is an important mechanism for maintaining tissue retinoids in a form that is easily stored and readily mobilized for additional metabolism (22).…”

The Tumor Suppressor Adenomatous Polyposis Coli and Caudal Related Homeodomain Protein Regulate Expression of Retinol Dehydrogenase L

“…In addition to the nuclear hormone receptors, retinoid responsiveness within cells is governed by retinoid availability (35,36). For the most part, cells acquire retinoids in the form of retinol, an inactive precursor.…”

“…Enzymes in each class have broad substrate specificities and can oxidize or reduce many physiologically important alcohols or aldehydes including ethanol, steroids, and retinoids. The actions of RA, in turn, can be limited by catabolism via cytochrome P450 enzymes (35,36). Although the biochemistry of these retinoid biosynthetic and metabolic enzymes is emerging, little is known about the regulation of these enzymes within tissues or specific cell types.…”