维生素是通过饮食获得的必需化合物,是生物体正常发育和功能所必需的。人体生理学最重要的维生素之一是维生素A,一组类维生素A化合物和类胡萝卜素,通常作为细胞生长的介质,分化,豁免权,和胚胎发育,以及作为脊椎动物视网膜光传导周期的关键组成部分。对于人类来说,维生素A是通过饮食获得的,其中维生素原A类胡萝卜素如来自植物的β-胡萝卜素或预先形成的维生素A如来自动物来源的视黄酯通过小肠被吸收到体内并在肠内细胞内转化为全反式视黄醇。具体来说,一旦吸收,类胡萝卜素被类胡萝卜素裂解加氧酶(CCOs)裂解,如β-胡萝卜素15,15'-单加氧酶(BCO1),产生全反式视黄醛,然后转化为全反式视黄醇。然后通过内质网中的卵磷脂视黄醇酰基转移酶(LRAT)将CRBP2结合的视黄醇转化为视黄酯(REs),然后将其包装成乳糜微粒并送入血液中,以储存在肝脏的肝星状细胞中或在视网膜等外周组织中使用。全反式视黄醇也通过与视黄醇结合蛋白4(RBP4)结合的血流,它在跨膜转运蛋白的帮助下进入细胞,外周组织中的视黄酸6(STRA6)或全身组织中的视黄醇结合蛋白4受体2(RBPR2)刺激(例如,在视网膜和肝脏中,分别)。人们对摄入量了解很多,新陈代谢,storage,和维生素A化合物的功能,特别是在类视黄醇循环中对眼睛发育和视觉功能的影响。然而,有很多关于维生素A作为转录因子在发育和细胞生长中的作用,以及外周细胞如何向肝细胞发出信号,将全反式视黄醇分泌到血液中用于外周细胞。本文旨在回顾有关从饮食来源摄入维生素A进入肝细胞的主要已知途径的文献。肝细胞排泄维生素A,以及维生素A在RPE和视网膜中的类维生素A循环中的使用,以提供有关新型膜转运蛋白在视网膜细胞生理学和视觉功能中的未来方向的见解。
Vitamins are essential compounds obtained through diet that are necessary for normal development and function in an organism. One of the most important vitamins for human physiology is vitamin A, a group of retinoid compounds and carotenoids, which generally function as a mediator for cell growth, differentiation, immunity, and embryonic development, as well as serving as a key component in the phototransduction cycle in the vertebrate retina. For humans, vitamin A is obtained through the diet, where provitamin A carotenoids such as β-carotene from plants or preformed vitamin A such as retinyl esters from animal sources are absorbed into the body via the small intestine and converted into all-trans retinol within the intestinal enterocytes. Specifically, once absorbed, carotenoids are cleaved by carotenoid cleavage oxygenases (CCOs), such as Beta-carotene 15,15\'-monooxygenase (BCO1), to produce all-trans retinal that subsequently gets converted into all-trans retinol. CRBP2 bound retinol is then converted into retinyl esters (REs) by the enzyme lecithin retinol acyltransferase (LRAT) in the endoplasmic reticulum, which is then packaged into chylomicrons and sent into the bloodstream for storage in hepatic stellate cells in the liver or for functional use in peripheral tissues such as the retina. All-trans retinol also travels through the bloodstream bound to retinol binding protein 4 (RBP4), where it enters cells with the assistance of the transmembrane transporters, stimulated by retinoic acid 6 (STRA6) in peripheral tissues or retinol binding protein 4 receptor 2 (RBPR2) in systemic tissues (e.g., in the retina and the liver, respectively). Much is known about the intake, metabolism, storage, and function of vitamin A compounds, especially with regard to its impact on eye development and visual function in the retinoid cycle. However, there is much to learn about the role of vitamin A as a transcription factor in development and cell growth, as well as how peripheral cells signal hepatocytes to secrete all-trans retinol into the blood for peripheral cell use. This article aims to
review literature regarding the major known pathways of vitamin A intake from dietary sources into hepatocytes, vitamin A excretion by hepatocytes, as well as vitamin A usage within the retinoid cycle in the RPE and retina to provide insight on future directions of novel membrane transporters for vitamin A in retinal cell physiology and visual function.