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Expression, structure‐function, and molecular modeling of vitamin D P450s
Author(s) -
Omdahl J.L.,
Bobrovnikova E.V.,
Annalora A.,
Chen P.,
Serda R.
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10366
Subject(s) - vitamin d and neurology , enzyme , biochemistry , chemistry , cyp24a1 , vitamin , cytochrome p450 , vitamin d binding protein , cytochrome , biology , calcitriol receptor , receptor , endocrinology
Although vitamin D 3 is a natural product of a sunlight‐mediated process in the skin, the secosteroid's biological function is dependent upon specific cytochrome P450 enzymes that mediate the parent vitamin's bioactivation and inactivation. Cytochrome P450C1 (CYP27B1) is the regulatory rate‐limiting enzyme that directs the bioactivation process through introduction of a C‐1α hydroxyl group. The resultant 1,25‐dihydroxyvitamin D 3 (1,25D) is the biologically active secosteroid hormone that directs the multitude of vitamin D‐dependent actions involved with calcium homeostasis, cellular differentiation and growth, and the immune response. The circulating and cellular level of 1,25D is regulated through a coordinated process involving the hormone's synthesis and degradation. Central to the degradation and turnover of 1,25D is the regulatory multi‐catalytic cytochrome P450C24 (CYP24) enzyme that directs the introduction of C‐24R groups onto targeted 25‐hydroxy substrates. Discussed in this article is the action of the rat CYP24 to catalyze the side‐chain oxidation and cleavage of 25‐hydroxylated vitamin D metabolites. Expression and characterization of purified recombinant rat CYP24 is discussed in light of mutations directed at the enzyme's active site. J. Cell. Biochem. 88: 356–362, 2003. © 2002 Wiley‐Liss, Inc.