Retinol, a primary alcohol, is present in animal tissues as a retinyl ester with long-chain fatty acids. It serves as the storage form of vitamin A. Retinal, derived from the oxidation of retinol, is the corresponding aldehyde and can be easily converted to retinol and vice versa. On the other hand, retinoic acid, which is derived from the oxidation of retinal, cannot be reduced in the body and therefore cannot be converted back to retinal or retinol.

Plant foods contain β-carotene, also known as provitamin A, which can be cleaved into two molecules of retinal through oxidative and symmetrical cleavage in the intestine. However, this conversion process is inefficient in humans, and the vitamin A activity of β-carotene is only about 1/12 that of retinol.

Retinyl esters obtained from the diet are hydrolyzed in the intestinal mucosa, releasing retinol and free fatty acids. Within the enterocytes, retinol is reesterified to long-chain fatty acids and secreted as part of chylomicrons into the lymphatic system. Chylomicron remnants containing retinyl esters are taken up by the liver for storage. It is important to note that all fat-soluble vitamins are transported in chylomicrons.

When needed, retinol is released from the liver and transported through the blood to peripheral tissues. This transport is facilitated by retinol-binding protein complexed with transthyretin. The ternary complex binds to a transport protein on the surface of peripheral tissue cells, allowing retinol to enter. Intracellular retinol-binding protein carries retinol to the nucleus, where it regulates transcription similar to steroid hormones.

Retinoic acid, formed by the oxidation of retinol, binds with high affinity to specific receptor proteins called retinoic acid receptors (RAR) found in the nucleus of target tissues such as epithelial cells. The activated retinoic acid-RAR complex binds to response elements on DNA and recruits activators or repressors to control retinoid-specific RNA synthesis. This regulation ultimately influences the production of specific proteins involved in various physiological functions. For example, retinoids control the expression of the keratin gene in most epithelial tissues of the body. It is worth mentioning that RAR proteins are part of the superfamily of transcriptional regulators, which also includes nuclear receptors for steroid and thyroid hormones and vitamin D. These regulators function in a similar manner.
Retinol: A primary alcohol containing a β-ionone ring with an unsaturated side chain, retinol is found in animal tissues as a retinyl ester with long-chain FA. It is the storage form of vitamin A.
2.
Retinal: This is the aldehyde derived from the oxidation of retinol. Retinal and retinol can readily be interconverted.
3.
Retinoic acid: This is the acid derived from the oxidation of retinal. Retinoic acid cannot be reduced in the body and, therefore, cannot give rise to either retinal or retinol.
4.
β-Carotene: Plant foods contain β-carotene (provitamin A), which can be oxidatively and symmetrically cleaved in the intestine to yield two molecules of retinal. In humans, the conversion is inefficient, and the vitamin A activity of β-carotene is only about 1/12 that of retinol.
B. Absorption and transport to the liver
Retinyl esters from the diet are hydrolyzed in the intestinal mucosa, releasing retinol and FFA (Fig. 28.19). Retinol derived from esters and from the reduction of retinal from β-carotene cleavage is reesterified to long-chain FA within the enterocytes and secreted as a component of chylomicrons into the lymphatic system. Retinyl esters contained in chylomicron remnants are taken up by, and stored in, the liver. [Note: All fat-soluble vitamins are carried in chylomicrons.]
C. Release from the liver
When needed, retinol is released from the liver and transported through the blood to extrahepatic tissues by retinol-binding protein complexed with transthyretin (see Fig. 28.19). The ternary complex binds to a transport protein on the surface of the cells of peripheral tissues, permitting retinol to enter. An intracellular retinol-binding protein carries retinol to sites in the nucleus where the vitamin regulates transcription in a manner analogous to that of steroid hormones.
D. Retinoic acid mechanism of action
Retinol is oxidized to retinoic acid. Retinoic acid binds with high affinity to specific receptor proteins (retinoic acid receptors [RAR]) present in the nucleus of target tissues such as epithelial cells (Fig. 28.20). The activated retinoic acid–RAR complex binds to response elements on DNA and recruits activators or repressors to regulate retinoid-specific RNA synthesis, resulting in control of the production of specific proteins that mediate several physiologic functions. For example, retinoids control the expression of the gene for keratin in most epithelial tissues of the body. [Note: The RAR proteins are part of the superfamily of transcriptional regulators that includes the nuclear receptors for steroid and thyroid hormones and vitamin D, all of which function in a similar way (see p. 240).]
E. Functions 1.