Preparation, properties and metabolism of retro-3-dehydroretinyl acetate

Abstract

1. Treatment of 3-dehydroretinyl acetate with aqueous hydrobromic acid resulted in the formation of retro-3-dehydroretinyl acetate, which, on alkaline hydrolysis, gave the corresponding alcohol. 2. retro-3-Dehydroretinyl acetate was isomerized to 3-dehydrovitamin A when fed to vitamin A-deficient rats. 3. When retro-3-dehydroretinyl acetate was administered orally, it was hydrolysed to retro-3-dehydroretinol in the rat intestine, isomerized to 3-dehydroretinol and esterified before being transported to the liver for storage. 4. When administered intraperitoneally, both 3-dehydrovitamin A and retro-3-dehydrovitamin A were accumulated in liver and other tissues, whereas after enterectomy 3-dehydrovitamin A was not detected anywhere in the body. 5. The small intestine was shown to be the major site of conversion of retro-3-dehydrovitamin A into 3-dehydrovitamin A. 6. The extent of conversion of retro-3-dehydroretinyl acetate into 3-dehydrovitamin A was much smaller than that of the conversion of retro-retinyl acetate into vitamin A. 7. The biological potency of retro-3-dehydroretinyl acetate, determined by the rat-growth assay, was 2.6% of that all-trans-retinyl acetate, when given orally.

Metabolism of 5,6-epoxyretinoic acid in vivo: isolation of a major intestinal metabolite

“…Moreover, under similar experimental circumstances, the metabolism of 5,6-epoxyretinoic acid in vivo is much more rapid than that of its precursor, retinoic acid. Consequently, estimates of 5,6-epoxyretinoic acid biological activity, especially obtained with in vivo assays, may be low (Morgan & Thompson, 1966;Mallia et al, 1970;Strickland, 1978;Adamo et al, 1979;Newton et al, 1980;Strickland & Mahdavi, 1980). The identity of the major 5,depoxyretinoic acid metabolite in the small intestinal mucosa and intestinal contents as 5,6epoxyretinoyl glucuronide is based on several facts.…”

“…The epoxide is also equipotent with retinoic acid in the induction of differentiation of cultured embryonal carcinoma cells (Strickland, 1978). However, the growth-promoting activity of 5,6-epoxyretinoic acid is well-known to be much less than that of retinoic acid (Morgan & Thompson, 1966;Mallia et al, 1970). The latter results may be attributable to pharmacological effects.…”