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Title: Metabolism of the cell differentiating agent 1alpha,25(OH)2-16-ene-23-yne vitamin D3 by leukemic cells. Author: Satchell DP, Norman AW. Journal: J Steroid Biochem Mol Biol; 1996 Jan; 57(1-2):117-24. PubMed ID: 8645610. Abstract: The metabolism of 1alpha,25(OH)2D3 and 1alpha,25(OH)2-l6-ene-23-yne-D3 is examined by in vitro incubation of the steroid hormones with WEHI-3 myeloid leukemia cells. Two experimental systems were used to evaluate the metabolism of each compound: (a) a double label incubation was performed to determine both the propensity for metabolism of each analog and the in vitro half-life of the analogs; and (b) separate single label incubations were performed to determine the metabolite profile derived from each of the analogs. The double label WEHI-3 cell incubation with 25 nM [23,24(3)H]1alpha,25(OH)2D3 and 25 nM [25(14)C]1alpha,25(OH)2-16-ene-23-yne-D3 produced a single comigrating metabolite of higher polarity from each of the parent compounds in a gradient HPLC chromatogram. The half-life of each analog determined from this in vitro incubation was 6.9 and 6.7 h for 1alpha,25(OH)2D3 and 1alpha,25(OH)2-16-ene-23-yne-D3, respectively. Individual incubations of 1alpha,25(OH)2D3 yielded a metabolite that comigrates with 1alpha,24,25(OH)2D3 standard in each of three independent HPLC separations. Individual incubations with [25(14)C]1alpha,25(OH)2-16-ene-23-yne-D3 generated multiple metabolites, which are resistant to degradation as evaluated by intermediate build-up, are of increasing polarity and do not comigrate with the 1alpha,24,25(OH)3D3 standard. From these studies it is determined that 1alpha,25(OH)2-l6-ene-23-yne-D3 is metabolized differently but not preferentially compared to 1,25(OH)2D3 in myelogenous leukemia cells.[Abstract] [Full Text] [Related] [New Search]