Retinaldehyde retinol conversion

Fig. 1. The structures of key retinoids and their precursors. Fish convert retinyl esters (e.g. retinyl palmitate (RP)) and carotenoids (e.g. /3-carotene) to retinol in the gut lumen prior to intestinal absorption. Retinyl esters (e.g. RP) stored in the liver are synthesized from retinol by lecithin retinol acyltransferase (LRAT) and acyl CoAiretinol acyltransferase (ARAT). The retinyl esters are mobilized through their conversion to retinol by retinyl ester hydrolase (REH), which is then transported in the circulation to various sites in the body. Retinol is further metabolized within specific tissues to retinal by alcohol dehydrogenases (ADH) or short-chain dehydrogenase/reductase. Retinal is converted to the two major biologically active forms of retinoic acid (RA) (all-trans and 9-cis RA). Retinaldehyde dehydrogenase 2 (Raldh2) synthesizes all-trans RA from all-trans precursors and 9-cis RA form 9-cis precursors.

In the retinal cells of the eye, vitamin A (all-trans-retinol) is converted into the 11-ds-isomer, which is then oxidised to 11-cts-retinaldehde. In the dark the latter then combines with the protein opsin to form rhodopsin (visual purple), which is the photoreceptor for vision at low light intensities. When light falls on the retina, the czs-retinaldehyde molecule is converted back into the aW-trans form and is released from the opsin. This conversion results in the transmission of an impulse up the optic nerve. The all-frans-retinaldehyde is converted to all-trans-retinol, which re-enters the cycle, thus continually renewing the light sensitivity of the retina (Rg. 5.2). 

The intestinal mucosa is not the only tissue that can enzymatically cleave P-carotene into retinaldehyde. Enzymatic activities with similar properties were observed in homogenate preparations of both rat liver and intestine by Olson and Hayaishi (1965). The conversion of P-carotene to retinaldehyde and retinol by slices of bovine corpus luteum has been reported (Gawienowski et al., 1974 Stacewicz-Sapuncakis et al., 1975). The potential physiological significance of this reaction in the corpus luteum remains to be determined. 

The metabolism of several other synthetic retinoids has been briefly examined but not analyzed to any great extent. Included are studies in rats of the hydrolysis of retinoic acid anhydride to retinoic acid (Premachandra and Cama, 1975), the conversion in hamsters of retinaldehyde acetylhydrazone (C8) and (V-acetyl-retinylamine (Bl) to retinol and retinyl esters (Roberts etal., 1978), the metabolism of 15-methyl retinone, 15-methylretinol, and 15,15-dimethylretinol (AlO) and the excretion of their metabolites in the bile and urine of rats (Tosukhowong and Olson, 1978), and the metabolism of 5,6-epoxy-5,6-dihydroretinol and retinaldehyde both in rats (Jungalwala and Cama, 1965 Lakshmanan et ai, 1965) and in cultured, spontaneously transformed mouse fibroblasts (Bhat et al., 1981). Because of the lack of extensive metabolic studies, these reactions are not discussed further here. 

---