UNIQUE 24-HYDROXYLATED METABOLITES REPRESENT A SIGNIFICANT PATHWAY OFMETABOLISM OF VITAMIN-D-2 IN HUMANS - 24-HYDROXYVITAMIN-D-2 AND 1,24-DIHYDROXYVITAMIN-D-2 DETECTABLE IN HUMAN SERUM

We have produced evidence for a new metabolic pathway for vitamin D-2 in humans involving the production of 24-hydroxyvitamin D-2 (240HD(2)) and 1,24-dihydroxyvitamin D-2 [1,24-(OH)2D(2)]. These metabolites wer e produced after either a single large dose (10(6) IU) of vitamin D-2 or repeated daily doses between 10(3) and 5 x 10(4) IU. We developed a ssay systems for the metabolites in human serum and showed that in som e chronically treated patients, the concentration of 1,24-(OH)(2)D-2 e qualled that of 1,25-(OH)(2)D-2 at about 100 pmol/L. The metabolites w ere identified by high performance liquid chromatography with diode ar ray spectrophotometry for 240HD, and by high resolution gas chromatogr aphy-mass spectrometry for 1,24-(OH)(2)D-2. We show that 1,24-(OH)(2)D -2 synthesis can be stimulated by PTH, indicating a renal origin for t his metabolite and postulate that it is formed from 240HD(2), which ma y be synthesized in liver. We conclude from this study that vitamin D- 2 gives rise to two biologically active products, 1,24-(OH)(2)D-2 and 1,25-(OH)(2)D-2, and that 1,24-(OH)(2)D-2 could be an attractive natur ally occurring analog of 1,25-(OH)(2)D-3 for clinical use.