Lecithin:retinol acyltransferase and retinyl esters: is balance the essence in carcinogenesis?

摘要

Retinol (vitamin A) is metabolized into many structurally related compounds with independent biological activities in different cell types.1 For example; esterification of retinol to retinyl esters is an important mechanism to maintain tissue retinoids, which allows for easy storage and mobilization for further metabo lism. Lecithin:retinol acyltransferase (LRAT) is a microsomal enzyme that catalyzes the esterification of all-trans-retinol to all-trans retinyl esters by transferring the acyl group from the sn-1 position of phosphatidylcholine (shown in Fig. 1). It is an essential reaction for the retinoid cycle in visual system and vitamin A status in the liver. Retinoic acid regulates two families of retinoid recep tors (RAR and RXR) that control the expression of a large number of genes involved in a multitude of biological processes. LRAT is a key enzyme involved in retinoid homeostasis and is regulated in response to retinoic acid. It also negatively regulates retinoic acid biosynthesis by diverting retinol away from oxidative activation. Mutations in LRAT have been associated with early-onset severe retinal dystrophy. Regulation of LRAT activity is tissue specific and is highly sensitive to exogenous sources of retinoids and vitamin A. Decreases in stored retinol leads to the decline in free retinol and its metabolite which produces a state of local retinoid deficiency despite adequate dietary vitamin A intake and liver storage.