Retinyl esters from animal-sourced foods (or synthesized for dietary supplements for humans and domesticated animals) are acted upon by retinyl ester hydrolases in the lumen of the small intestine to release free retinol. Retinol enters intestinal absorptive cells by passive diffusion. Absorption efficiency is in the range of 70 to 90%. Humans are at risk for acute or chronic vitamin A toxicity because there are no mechanisms to suppress absorption or excrete the excess in urine. Within the cell, retinol is there bound to retinol binding protein 2 (RBP2). It is then enzymatically reesterified by the action of lecithin retinol acyltransferase and incorporated into chylomicrons that are secreted into the lymphatic system.
Unlike retinol, β-carotene is taken up by enterocytes by the membrane transporter protein scavenger receptor B1 (SCARB1). The protein is upregulated in times of vitamin A deficiency. If vitamin A status is in the normal range, SCARB1 is downregulated, reducing absorption. Also downregulated is the enzyme beta-carotene 15,15-dioxygenase (formerly known as beta-carotene 15,15-monooxygenase) coded for by the BCMO1 gene, responsible for symmetrically cleaving β-carotene into retinal. Absorbed β-carotene is either incorporated as such into chylomicrons or first converted to retinal and then retinol, bound to RBP2. After a meal, roughly two-thirds of the chylomicrons are taken up by the liver with the remainder delivered to peripheral tissues. Peripheral tissues also can convert chylomicron β-carotene to retinol.
The capacity to store retinol in the liver means that well-nourished humans can go months on a vitamin A deficient diet without manifesting signs and symptoms of deficiency. Two liver cell types are responsible for storage and release: hepatocytes and hepatic stellate cells (HSCs). Hepatocytes take up the lipid-rich chylomicrons, bind retinol to retinol-binding protein 4 (RBP4), and transfer the retinol-RBP4 to HSCs for storage in lipid droplets as retinyl esters. Mobilization reverses the process: retinyl ester hydrolase releases free retinol which is transferred to hepatocytes, bound to RBP4, and put into blood circulation. Other than either after a meal or when consumption of large amounts exceeds liver storage capacity, more than 95% of retinol in circulation is bound to RBP4.