Structure and functions of human oxysterol 7 alpha-hydroxylase cDNAs and gene CYP7B1

Structure and functions of human oxysterol 7 alpha-hydroxylase cDNAs and gene CYP7B1

Wu Z L; Martin K O; Javitt N B; Chiang J Y L

Journal of Lipid Research

1999

1999-12

Oxysterol 7 alpha-hydroxylase has broad substrate specificity for sterol metabolites and may be involved in many metabolic processes including bile acid synthesis and neurosteroid metabolism, The cloned human oxysterol 7 alpha-hydroxylase (CYP7B1) cDNA encodes a polypeptide of 506 amino acid residues that shares 40% sequence identity to human cholesterol 7 alpha-hydroxylase (CW7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver. In contrast to the liver-specific expression of CYP7A1, CYP7B1 mRNA transcripts were detected in human tissues involved in steroid genesis (brain, testes, ovary, and prostate) and in bile acid synthesis (liver) and reabsorption (colon, kidney, and small intestine). The human oxysterol 7 alpha-hydroxylase transiently expressed in 293/T cells was able to catalyze 7 alpha-hydroxylation of 27-hydroxycholesterol and dehydroepiandrosterone (DHEA), The human CYP7A1 and CYP7B1 both contain six exons and five introns. However, CPP7B1 spans at least 65 kb of the genome and is about 6-fold longer than CYP7A1. The transcription start site (+1) was localized 204 bp upstream of the initiation codon, No TATA box-like sequence was found near the transcription start site. Transient transfection assays of CYP7B1 promoter/luciferase reporter constructs in HepG2 cells revealed that the promoter was highly active. The 5' upstream region from nt -83 to +189 is the core promoter of the gene.

27-hydroxycholesterol; 7-alpha-hydroxylase; bile-acid synthesis; bile-acid synthesis; Biochemistry & Molecular Biology; brain; cholesterol; cholesterol 7 alpha-hydroxylase; cytochrome P450; cytochrome P450; dehydroepiandrosterone (DHEA); dehydroepiandrosterone (DHEA); human liver-microsomes; identification; neurosteroids; transcription

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Journal Article

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2195-2203

12

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