Some aspects of the metabolism and biochemistry of vitamin A.

The metabolism of vitamin A Formation of retinof, retinyl esters and retinal. Dietary provitamins and vitamin A are sources of tissue deposits of retinol, retinyl esters and retinal; the latter substances constitute a storage and transport system (Ganguly, 1960) which allows a continuous supply of the active form of the vitamin to be provided at whatever site it is required. T h e alcohol, aldehyde and esters are readily interconverted enzymically, and intake of one particular form of the vitamin in the diet is followed by in vivo conversion into the others. Oxidation of retinol to retinal is catalysed by alcohol dehydrogenase enzymes of wide distribution (Glover, Goodwin & Morton, 1948; Wald & Hubbard, 1948-9; Bliss, 1951; Futterman & Saslaw, 1961). In rod outer segments, the reduction of retinal utilizes principally NADPH as cofactor (Futterman, I 963). Retinal is the active form of vitamin A in vision, being the prosthetic group of the visual pigments (Hubbard & Kropf, 1959); its occurrence outside the retina implies that it might have other unsuspected functions (Plack, Kon & Thompson, 1958, 1959; Pollard & Bieri, 1959; Plack, 1960; Winterstein & Hegediis, 1960). The role of vitamin A in vision has been reviewed recently (Wald, 1960) and will not be considered here. This aspect of vitamin A biochemistry and metabolism, however, is probably ‘better understood by far than any other major function of the fat soluble vitamins’ (Pitt & Morton, 1962). Formation of retinoic acid. Retinoic acid and its esters were first obtained during attempts at the chemical synthesis of retinol (Heilbron, Jones, Lowe &Wright, 1936; van Dorp & Arens, 1946~). Subsequent discovery of the comparatively high biological activity of the free acid in rat growth tests (van Dorp & Arens, 194623) without its being reduced in vivo to retinol (Arens & van Dorp, 1946; Sharman, 1949) encouraged the speculation that retinoic acid was a metabolite of retinol, and was a precursor of, or was itself, the systemically active form of vitamin A (Dowling & Wald, 1960). It has been shown that enzymic oxidation of retinal to retinoic acid can occur in vitro (Futterman, 1962; Mahadevan, Murthy & Ganguly, 1962; Elder & Topper, I 962), and thus the suggested formation of retinoic acid in vivo is biochemically feasible ; whether the biological effect of this conversion is quantitatively significant, however, remains in doubt. Dmitrovsky (1961) detected retinoic acid in the jejunum of rats given by mouth 20 mg retinal; but retinoic acid could not be detected in intestine, blood or liver of chicks given 3 mg retinal (Krishnamurthy, Bieri & Andrews,