Overview of regulatory cytochrome P450 enzymes of the vitamin D pathway

Citation
Jl. Omdahl et al., Overview of regulatory cytochrome P450 enzymes of the vitamin D pathway, STEROIDS, 66(3-5), 2001, pp. 381-389
Citations number
71
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
STEROIDS
ISSN journal
0039-128X → ACNP
Volume
66
Issue
3-5
Year of publication
2001
Pages
381 - 389
Database
ISI
SICI code
0039-128X(200103/05)66:3-5<381:OORCPE>2.0.ZU;2-Z
Abstract
Cytochromes P450c1 and P450c24 are regulated hydroxylase enzymes that direc t the bioactivation and metabolic degradation of vitamin D. The bioactivati on pathway is regulated by cytochrome p450c1 through its synthesis of 1 alp ha ,25(OH)(2)D-3, the hormonally active form of the vitamin. Expression of the P450c1 gene is regulated at the transcription level, promoter regions w ithin the P450c1 gene have been identified that respond to cAMP and 1 alpha ,25(OH)(2)D-3 during the respective up- and down-regulation of P450c1 gene expression. The diametric action of 1 alpha ,25(OH)(2)D-3 to up-regulate P 450c24 gene expression is discussed in the context of two vitamin D respons e elements (VDREs) that are linked functionally to an adjoining Ets-binding site. It is apparent from sequence-derived data that the P450c1 and P450c2 4 enzymes share only 10-25% sequence identity, yet they display functionall y similar domains that are conserved across the family of cytochrome P450 e nzymes. Expression of E. coli recombinant P450c1 and P450c24 enzymes, and t he substrate-binding parameters for P450c24 are discussed. Finally, the nat ural point mutations in human P540c1 from patients with pseudovitamin D-def iciency rickets (PDDR) are discussed in the context of the enzyme's structu re and function. (C) 2001 Elsevier Science Inc. All rights reserved.