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.