Retinaldehyde reductase

Retinal is reduced to retinol by retinaldehyde reductase, an NADPH requiring enzyme within the intestines. 

Dalf6, D., N. Marques, and R. Albalat. 2007. Analysis of the Nadh-Dependent Retinaldehyde Reductase Activity of Amphioxus Retinol Dehydrogenase Enzymes Enhances Our Understanding of the Evolution of the Retinol Dehydrogenase Family. Febs J 274, no 14 3739-52. 

Among humans, abnormal dark adaptation is reported in both vitamin A deficiency and zinc deficiency and is especially prevalent in alcoholic cirrhotics (Patek and Haig, 1939 Russell et aL, 1973 Morrison et aL, 1978 McClain et aL, 1979). In the former but not in the latter deficiency, treatment with vitamin A reverses the abnormality (Russell et aL, 1978) only after correcting the zinc deficiency does dark adaptation become normal in the latter case (Morrison et aL, 1978 McClain et aL, 1979). The molecular basis for these observations may be associated, at least in part, with the activity of retinaldehyde reductase in the retina which, as already mentioned, Huber and Gershoff (1975) showed to be especially sensitive to the level of zinc nutriture and Mezey and Holt (1971) showed was competitively inhibited by the presence of ethanol. In the alcoholic cirrhotic, however, the zinc-vitamin A interaction may be further complicated by a defective hepatic synthesis of transport proteins (Mobarhan et aL, 1981) or failure to sequester or retain zinc Nutrition Reviews, 1982) and/or vitamin A (Sato and Lieber, 1981 Leo and Lieber, 1982) in the appropriate tissues. The implications for human nutrition of the interaction of vitamin A and zinc were reviewed by Solomons and Russell (1980). 

The major natural sources of vitamin A in the diet are certain plant carotenoid pigments, such as p-carotene, and the long-chain retinyl esters found in animal tissues. p-Carotene is converted to vitamin A primarily in the intestinal mucosa. The biosynthetic process involves two soluble enzymes p-carotene 15,15 -diox-ygenase and retinaldehyde reductase. The first enzyme catalyzes the cleavage of P-carotene at the central double bond by a dioxygenase mechanism to yield two molecules of retinaldehyde (Cl) the aldehyde is then reduced to retinol (Al). 

Retinaldehyde, when bound to retinol binding protein II (CRBPII), serves as a substrate for retinal reductase resulting in the production of retinol (14), which then binds to cellular retinol binding protein (CRBP) forming holo-CRBP. Holo-CRBP seems to be the preferred substrate for an esterification reaction (Fig. 7.6) mediated by lecithin retinol acyl transferase (LRAT), a microsomal enzyme that uses acyl groups donated from phosphatidylcholine (14).In cells not expressing CRBP, retinol esterification is carried out by a different enzyme, acyl CoArretinol acyl transferase (ARAT). 

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.

The reduction of retinaldehyde to retinol was studied with an approximately 13-fold purified soluble enzyme preparation from rat intestinal mucosa (Fidge and Goodman, 1968). The enzyme was relatively heat stable and had a molecular weight approximately in the range of 60,000-80,000. The partly purified reductase was unable to oxidize ethanol in the presence of NAD" ". Retinaldehyde reduction required NADH or NADPH as cofactor both reduced nucleotides were effective. The reaction was stimulated by glutathione and inhibited by thiol inhibitors. There was a sharp pH optimum near 6.3. Retinaldehyde reduction displayed typical Michaelis kinetics, with a 2 xmol of retinol formed per... 

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