Abstract |
It is known that phagocytic cells such as monocyte-macrophages and myeloid leukemia cells metabolize 25-hydroxyvitamin D3 to 10-oxo-19-nor-25-hydroxyvitamin D3. Now we have found that phagocytic cells metabolize 25-hydroxyvitamin D3 not only to 10-oxo-19-nor-25-hydroxyvitamin D3 but also to a new metabolite eluted just after 24R,25-dihydroxyvitamin D3 on straight phase high pressure liquid chromatography with a 2-propanol-hexane solvent system. The new metabolite, produced by murine myeloid leukemia cells (M1), was isolated in pure form and identified as 8,25-dihydroxy-9,10-seco-4,6,10(19)-cholestatrien-3-one on the basis of mass, ultraviolet, infrared, and proton magnetic resonance spectra. The 8 alpha-hydroxy epimer of the putative metabolite was chemically synthesized in two steps starting from 25-hydroxyvitamin D3. The spectral data and chromatographic behavior of chemically synthesized 8 alpha,25-dihydroxy-9,10-seco-4,6,10(19)-cholestatrien-3-one coincided exactly with those of the isolated metabolite, indicating that the stereochemistry of the hydroxyl group at the 8-position is alpha. On the basis of the structural characteristics of the two metabolites produced from 25-hydroxyvitamin D3 (the present metabolite and 10-oxo-19-nor-25-hydroxyvitamin D3), it is suggested that dioxygenases are involved in the production of these metabolites from 25-hydroxyvitamin D3 in phagocytic cells.
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Authors | S Yamada, K Yamamoto, H Takayama, T Hayashi, C Miyaura, H Tanaka, E Abe, T Suda |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 262
Issue 27
Pg. 12939-44
(Sep 25 1987)
ISSN: 0021-9258 [Print] United States |
PMID | 3477540
(Publication Type: Journal Article)
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Chemical References |
- Cholestenes
- Indicators and Reagents
- 8,25-dihydroxy-9,10-seco-4,6,10(19)-cholestatrien-3-one
- Calcifediol
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Topics |
- Animals
- Calcifediol
(metabolism)
- Cholestenes
(chemical synthesis, isolation & purification)
- Chromatography, High Pressure Liquid
- Indicators and Reagents
- Leukemia, Experimental
(metabolism)
- Leukemia, Myeloid
(metabolism)
- Magnetic Resonance Spectroscopy
- Mass Spectrometry
- Mice
- Spectrophotometry, Ultraviolet
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