Isolation and identification of 5, 6-epoxyretinoic acid: a biologically active metabolite of retinoic acid.

A highly biologically active metabolite of retinoic acid (8III) has been isolated in pure form from intestinal mucosa of vitamin A deficient rats given [3H]retinoic acid. This metabolite has been positively identified as 5, 6-epoxyretinoic acid based on the ultraviolet absorption spectrum and mass spectrum of its methylated derivative. This identification was confirmed by cochromatography of the methylated metabolite and synthetic methyl 5, 6-epoxyretinoate on reverse-phase and straight-phase high-pressure liquid chromatography. The 5, 6-epoxyretinoic acid is a true in vivo generated metabolite of retinoic acid and not an artifact of the isolation procedure. In addition, 5, 8-oxyretinoic acid previously isolated in this laboratory from intestinal mucosa was probably generated from 5, 6-epoxyretinoic acid by the acidic conditions used in the extraction and isolation of the 5, 8-oxyretinoic acid.

[1]  H. DeLuca,et al.  Effect of vitamin A deficiency on intestinal cell proliferation in the rat. , 1977, The Journal of nutrition.

[2]  G. P. Tryfiates,et al.  The effect of retinol and retinoic acid on physiological and biochemical changes in retinol-deficient rats , 1975, British Journal of Nutrition.

[3]  H. DeLuca,et al.  Metabolism of retinoic acid in vitamin A-deficient rats , 1974 .

[4]  L. D. De Luca,et al.  Maintenance of epithelial cell differentiation: The mode of action of vitamin A , 1972, Cancer.

[5]  H. DeLuca,et al.  Vitamin A and ribonucleic acid synthesis in rat intestine. , 1970, Archives of biochemistry and biophysics.

[6]  B. Johnson,et al.  Vitamin A and nuclear RNA synthesis. , 1969, The American journal of clinical nutrition.

[7]  G. Wolf,et al.  Vitamin A and protein synthesis in mucous membranes. , 1969, The American journal of clinical nutrition.

[8]  G. Wolf,et al.  Vitamin A and protein synthesis by rat intestinal mucosa. , 1969, The Journal of biological chemistry.

[9]  H. DeLuca,et al.  Retinoic acid: some aspects of growth-promoting activity in the albino rat. , 1968, The Journal of nutrition.

[10]  R. Zachman.  The stimulation of RNA synthesis in vivo and in vitro by retinol (vitamin A) in the intestine of vitamin A deficient rats. , 1967, Life sciences.

[11]  H. R. Cama,et al.  Preparation, properties and metabolism of 5,6-monoepoxyretinoic acid. , 1967, The Biochemical journal.

[12]  Krause,et al.  Biosynthesis of retinoic acid by intestinal enzymes of the rat. , 1967, Journal of lipid research.

[13]  R. J. Emerick,et al.  Formation of retinoic acid from retinol in the rat. , 1967, The Biochemical journal.

[14]  H. DeLuca,et al.  Pathways of retinol and retinoic acid metabolism in the rat. , 1967, The Biochemical journal.

[15]  J. Thompson,et al.  The preparation and biological activity of methyl 5,6-epoxy-retinoate. , 1966, The Biochemical journal.

[16]  P. Malathi,et al.  Rapid conversion of retinal (vitamin A aldehyde) to retinoic acid (vitamin A acid) in the living rat. , 1965, Biochimica et biophysica acta.

[17]  J. Thompson,et al.  Vitamin A and reproduction in rats , 1964, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[18]  P. Malathi,et al.  Studies on metabolism of vitamin A. 1. The biological activity of vitamin A acid in rats. , 1963, The Biochemical journal.

[19]  J. G. Bieri,et al.  Metabolism and biological activity of vitamin A acid in the chick. , 1963, The Journal of nutrition.

[20]  H. S. Teague,et al.  Effect of vitamin A intake on some biochemical and physiological changes in swine. , 1962, The Journal of nutrition.

[21]  J. Dowling,et al.  THE BIOLOGICAL FUNCTION OF VITAMIN A ACID. , 1960, Proceedings of the National Academy of Sciences of the United States of America.

[22]  H. DeLuca,et al.  Formation of retinoic acid from retinol in the kidney. , 1971, Archives of biochemistry and biophysics.

[23]  N. Fidge,et al.  Pathways of absorption of retinal and retinoic acid in the rat. , 1968, Journal of lipid research.