title: 1 alpha,24(S)-dihydroxyvitamin D2: a biologically active product of 1 alpha-hydroxyvitamin D2 made in the human hepatoma, Hep3B.
abstract: A major metabolite of the vitamin D analogue 1 alpha-hydroxyvitamin D2 in human liver cells in culture has been identified as 1 alpha,24(S)-dihydroxyvitamin D2 [1 alpha,24(S)-(OH)2D2]. 1 alpha-Hydroxyvitamin D3 incubated with the same cells gives rise to predominantly 25- and 27-hydroxylated products. Our identification of 1 alpha,24(S)-dihydroxyvitamin D2 is based on comparisons of the liver cell metabolite with chemically synthesized 1 alpha,24(S)-(OH)2D2 and 1 alpha,24(R)-(OH)2D2 by using HPLC, GC and GC-MS techniques. The stereochemical orientation of the 24-hydroxyl group was inferred after X-ray-crystallographic analysis of the 24(R)-OH epimer. 1 alpha,24(S)-Dihydroxyvitamin D2 binds strongly to the vitamin D receptor and is biologically active in growth hormone and chloramphenicol acetyltransferase reporter gene expression systems in vitro, but binds poorly to rat vitamin D-binding globulin, DBP. We suggest that this metabolite, 1 alpha,24(S)-(OH)2D2, possesses the spectrum of biological properties to be useful as a drug in the treatment of psoriasis, metabolic bone disease and cancer.
authors.affiliation: Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Strugnell
authors.forename: V
authors.initials: V
authors.lastname: Byford
authors.forename: H L
authors.initials: HL
authors.lastname: Makin
authors.forename: R M
authors.initials: RM
authors.lastname: Moriarty
authors.forename: R
authors.initials: R
authors.lastname: Gilardi
authors.forename: L W
authors.initials: LW
authors.lastname: LeVan
authors.forename: J C
authors.initials: JC
authors.lastname: Knutson
authors.forename: C W
authors.initials: CW
authors.lastname: Bishop
authors.forename: G
authors.initials: G
authors.lastname: Jones
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D002522:Chlorocebus aethiops; D004872:Ergocalciferols / Q000737:chemistry / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D017930:Genes, Reporter; D006801:Humans; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
chemical_list: D004872:Ergocalciferols; D018167:Receptors, Calcitriol; C063087:1,24-dihydroxyvitamin D2; C042533:1 alpha-hydroxyergocalciferol; D015500:Chloramphenicol O-Acetyltransferase