Abstract

The ability to store and distribute vitamin A inside the body is the main evolutionary adaptation that allows vertebrates to maintain retinoid functions during nutritional deficiencies and to acquire new metabolic pathways enabling light-independent production of 11-cis retinoids. These processes greatly depend on enzymes that esterify vitamin A as well as associated retinoid binding proteins. Although the significance of retinyl esters for vitamin A homeostasis is well established, until recently, the molecular basis for the retinol esterification enzymatic activity was unknown. In this review, we will look at retinoid absorption through the prism of current biochemical and structural studies on vitamin A esterifying enzymes. We describe molecular adaptations that enable retinoid storage and delineate mechanisms in which mutations found in selective proteins might influence vitamin A homeostasis in affected patients.

Highlights

  • Vitamin A is an essential fat-soluble nutrient with a pivotal role in various metabolic and physiological processes within the body [1,2]

  • We summarize the current knowledge regarding absorption, storage, and mobilization of vitamin A with special emphasis on new insights for molecular mechanisms of vitamin A esterification gained through advances of structural biology

  • The significance of retinol-binding protein (RBP)-mediated vitamin A transport is underscored by the fact that in a fasting state more than 95% of total retinol present in the blood serum is found in RBP-bound form

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Summary

Introduction

Vitamin A is an essential fat-soluble nutrient with a pivotal role in various metabolic and physiological processes within the body [1,2]. Unlike other fat-soluble vitamins, for which relatively small amounts (several pmol/g) can be found predominantly in the body’s adipose tissues, vitamin A can be stored in high quantities ranging between 10–1000 nmol/g mainly in liver and in kidneys and lungs [22]. This pool of retinoids exists mostly in the form of chemically inert REs and can be mobilized depending on the body’s demand for vitamin A [23,24,25]. A requires identification of the key protein components involved in these processes (Figure 1)

Role of Vitamin A Esterification in the Intestinal Uptake
LRAT Activity in Hepatic Retinoid Metabolism
Role of REs in the Ocular Metabolism of Retinoids
Insight intochoice
Structural Insight into Functional Adaptation of LRAT
Mutations in LRAT Gene and Their Clinical Manifestations
Role of LRAT in the General Retinoid Homeostasis
Synthesis of REs Incorporated into Milk
Eye Phenotype in LRAT-Deficiencies
Clinical Manifestation of Mutations in LRAT Gene
Findings
Conclusions and Future Directions
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