Unique 24-hydroxylated metabolites represent a significant pathway of metabolism of vitamin D2 in humans:: 24-hydroxyvitamin D2 and 1,24-dihydroxyvitamin D2 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 were 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 assay systems for the metabolites in human serum and showed that in some chronically treated patients, the concentration of 1,24-(OH)(2)D-2 equalled that of 1,25-(OH)(2)D-2 at about 100 pmol/L. The metabolites were identified by high performance liquid chromatography with diode array spectrophotometry for 240HD, and by high resolution gas chromatography-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 this metabolite and postulate that it is formed from 240HD(2), which may 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 naturally occurring analog of 1,25-(OH)(2)D-3 for clinical use.