Working Paper Review Version 1 This version is not peer-reviewed

Vitamin A Transporters in Visual Function: A Mini Review on Membrane Receptors for dietary Vitamin A Uptake, Storage, and Transport to the Eye

Version 1 : Received: 8 October 2021 / Approved: 11 October 2021 / Online: 11 October 2021 (14:15:27 CEST)

How to cite: Martin Ask, N.; Leung, M.; Radhakrishnan, R.; Lobo, G. Vitamin A Transporters in Visual Function: A Mini Review on Membrane Receptors for dietary Vitamin A Uptake, Storage, and Transport to the Eye. Preprints 2021, 2021100164 Martin Ask, N.; Leung, M.; Radhakrishnan, R.; Lobo, G. Vitamin A Transporters in Visual Function: A Mini Review on Membrane Receptors for dietary Vitamin A Uptake, Storage, and Transport to the Eye. Preprints 2021, 2021100164

Abstract

Vitamins are essential compounds obtained through diet that are necessary for normal devel-opment 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 vertebrate retina. For humans, vitamin A is obtained through the diet, where provitamin A carotenoids like β-carotene, or preformed vitamin A such as retinyl esters 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 carote-noid cleavage oxygenases (CCOs), such as 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 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 re-garding 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.

Keywords

vitamin A transporters; all-trans retinol; retinyl esters; LRAT; STRA6; RBPR2; RBP4; retinol-binding proteins; photoreceptors; visual function

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