## 3 Vitamin A, Its Vitaminoids and Carotenoids' General Profile and Health Benefits
### Vitamin A-Related Bioactive Compounds: Provitamins (Carotenoids)
#### 4.1.1 Oral Absorption and Metabolism of Vitamin A, Its Vitaminoids, and Carotenoids  
Vitamin A is primarily absorbed through the gastrointestinal (GI) tract when consumed orally, while vitamin A and its vitaminoids' absorption highly differs from that of carotenoids, indicated by the fact that animal-derived retinyl esters are almost completely absorbed, while plant-based carotenoids' absorption is notably lower [3; 87]. As for animal-derived vitamin A and its vitaminoids, predominantly retinyl esters, they reach the intestine, where their metabolization into retinol by a triglyceride lipase or phospholipase B in the intestinal lumen of the GI tract occurs. After being metabolized, retinol and retinoids penetrate into enterocytes along with \(\beta\)-carotene, associate with chylomicrons (ChM), and are finally secreted into the lymphatic system. The uptake of retinol may be initiated either by active transport or by passive diffusion, while fat-soluble retinol's absorption is increased after consuming fatty meals and micronutrients like zinc, as micelle formation encourages it. Both preformed retinol and retinol occurring from \(\beta\)-carotene transform into retinal, then to retinyl esters, and lastly to retinol, binding to a specific protein, namely cellular retinol-binding protein (CRBP), which is responsible for their intracellular transport and is acquired in two forms: CRBPI (widely expressed) and CRBPII, exclusively expressed in intestinal cells [3; 87; 88]. Retinol bound to CRBP while in the enterocytes may either be transformed back to retinyl esters bound to ChM and continue its path in the lymphatic system (cascade 1) or be transported directly in the blood systemic circulation via ChM's assistance, with retinol binding to the retinol-binding protein (Retinol-RBP) (cascade 2). More specifically, following cascade 1, ChM-bound retinyl esters first enter the lymphatic system and then the bloodstream as remnant chylomicrons-retinyl esters (RChM-retinyl esters), where again two different vitamin A pathways are likely to be induced: In the first pathway (cascade 3), RChM-retinyl esters enter the liver, the main retinoid storage body organ with the most vital retinoid-storing tissues/cells. Inside the liver, in the presence of hepatocytes and via the assistance of the RBP, retinyl esters are transformed into retinol and vice versa (\"recycling\"). Liver-derived retinol and preformed enterocyte-derived retinol are directly secreted into the bloodstream, where they bind to the RBP, transthyretin (thyroid hormone transport function) [89], or later on to other transport proteins like ATRA-bound albumin. Retinols'transportation in the target tissues is facilitated by the RBP receptor (RBPR), basically the \"gate\" to the target cell. Vitamin A deficiency is able to be maintained due to stored reserves in the liver (-90%), while circulating retinoids are usually bound to proteins like albumin via the mediation of lipoprotein receptors or stimulation by the retinoic acid 6 receptor (STRA6) [3,87,88]. During the second pathway (cascade 4), RChM-retinyl esters bind directly to the lipoprotein receptor (LR), which is reportedly another \"gate\" to the target cell, and undergo another conversion to retinol. RBPR and LR-acquired retinol are further oxidized to ATRA, and via the nuclear receptors (NRs), all necessary genetic body functions of vitamin A are initiated (the biochemical vitamin A-related function will be clarified in Section 4.2) [3,16,77,87,88,90]. The cellular and metabolic pathway of orally given vitamin A and its transportation to target cells is depicted in Figure 4.  
Retinyl esters, primarily retinyl palmitate, before even entering the enterocytes while in the intestinal lumen, are reversibly converted by esterase into retinol. Retinol, in order to biochemically participate in gene regulation and ROS scavenging, must be previously transformed into ATRA, which interacts with the NRs.