Retinol and retinyl esters: biochemistry and physiology

Abstract

The different retinoid forms present within the body (see Fig. 1 ) are generated by and large through modifi cations to the terminal polar end group of the molecule. Retinol and retinyl esters are the most abundant retinoid forms present in the body. All-trans -retinol is by defi nition vitamin A. When a fatty acyl group is esterifi ed to the hydroxyl terminus of retinol, a storage form of retinol, the retinyl ester, is formed. The most abundant retinyl esters present in the body are those of palmitic acid, oleic acid, stearic acid, and linoleic acid ( 6, 7 ). Although retinyl acetate can be found in supplements to foods and vitamin formulations, only long-chain acyl groups are esterifi ed to retinol by animals. Retinyl esters have no known biological activity aside from retinol storage and for serving as the substrate for the formation of the visual chromophore 11-cis -retinal, which must be formed from all-trans -retinyl ester through linked hydrolysis and isomerization reactions catalyzed by the enzyme RPE65 ( 3,4,8,9 ). Retinol is a transport form and a precursor form, which is enzymatically activated to retinoic acid via a two-step oxidation process. The primary role of retinal is in the eye where 11-cis -retinal is needed for visual pigment formation. In tissues, retinal serves as an intermediate in the synthesis of retinoic acid from retinol ( 6, 7 ). The literature also suggests a direct role for retinal in adipose tissue, where it was shown to inhibit adipogenesis and suppress peroxisome proliferator-activated receptor-␥ (PPAR ␥ ) and retinoid X receptor (RXR) responses in cell culture models and in mouse models fed high-fat diets ( 10 ).Abstract By defi nition, a vitamin is a substance that must be obtained regularly from the diet. Vitamin A must be acquired from the diet, but unlike most vitamins, it can also be stored within the body in relatively high levels. For humans living in developed nations or animals living in present-day vivariums, stored vitamin A concentrations can become relatively high, reaching levels that can protect against the adverse effects of insuffi cient vitamin A dietary intake for six months, or even much longer. The ability to accumulate vitamin A stores lessens the need for routinely consuming vitamin A in the diet, and this provides a selective advantage to the organism. The molecular processes that underlie this selective advantage include effi cient mechanisms to acquire vitamin A from the diet, effi cient and overlapping mechanisms for the transport of vitamin A in the circulation, a specifi c mechanism allowing for vitamin A storage, and a mechanism for mobilizing vitamin A from these stores in response to tissue needs. These processes are considered in this review. Since the identifi cation of fat-soluble A a century ago ( 1 ), retinoids (vitamin A and its natural and synthetic analogs) have been the most extensively studied of the fatsoluble vitamins. This research has identifi ed essential roles for retinoids in many different aspects of mammalian physiology, includ...

Genetic dissection of retinoid esterification and accumulation in the liver and adipose tissue

“…We investigated these possibilities in matched male WT, Lrat ( 44 ), the cellular site for RE storage in the liver ( 7,8,10 ). These investigators also reported that ablation of Dgat1 expression in cultured cells using antisense oligonucleotides results in increased expression of Lrat ( 44 ).…”

Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis

“…The pathways and general principles of intestinal absorption of dietary vitamin K into the enterocytes, packaging into chylomicrons, secretion into lymph lacteals, and entry into the blood via the thoracic duct are common for all fat-soluble vitamins ( 35,36 ). Within the vitamin K family, much more is known about the absorption and metabolic fate of K 1 than for MKs.…”

Scientific Opinion on Dietary Reference Values for vitamin A

“…The delivery of retinoids to tissues involves many different forms and carriers (Paik et al, 2004;O'Byrne and Blaner, 2013). Quantitatively the two most important pathways are those involving retinol bound to RBP4 and the postprandial delivery pathway.…”