Wu Z, Martin K O, Javitt N B, Chiang J Y
Department of Biochemistry and Molecular Pathology, Northeastern Ohio Universities College of Medicine, P. O. Box 95, Rootstown, OH 44272, USA.
J Lipid Res. 1999 Dec;40(12):2195-203.
Oxysterol 7alpha-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 7alpha-hydroxylase (CYP7B1) cDNA encodes a polypeptide of 506 amino acid residues that shares 40% sequence identity to human cholesterol 7alpha-hydroxylase (CYP7A1), 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 7alpha-hydroxylase transiently expressed in 293/T cells was able to catalyze 7alpha-hydroxylation of 27-hydroxycholesterol and dehydroepiandrosterone (DHEA). The human CYP7A1 and CYP7B1 both contain six exons and five introns. However, CYP7B1 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.
氧化甾醇7α-羟化酶对甾醇代谢产物具有广泛的底物特异性，可能参与包括胆汁酸合成和神经甾体代谢在内的许多代谢过程。克隆的人氧化甾醇7α-羟化酶（CYP7B1）cDNA编码一个由506个氨基酸残基组成的多肽，该多肽与人类胆固醇7α-羟化酶（CYP7A1）具有40%的序列同一性，CYP7A1是肝脏中胆固醇转化为胆汁酸的限速酶。与CYP7A1的肝脏特异性表达不同，在参与类固醇生成的人体组织（脑、睾丸、卵巢和前列腺）以及胆汁酸合成（肝脏）和重吸收（结肠、肾脏和小肠）中检测到了CYP7B1 mRNA转录本。在293/T细胞中瞬时表达的人氧化甾醇7α-羟化酶能够催化27-羟胆固醇和脱氢表雄酮（DHEA）的7α-羟化。人CYP7A1和CYP7B1都包含六个外显子和五个内含子。然而，CYP7B1跨越至少65 kb的基因组，比CYP7A1长约6倍。转录起始位点（+1）位于起始密码子上游204 bp处。在转录起始位点附近未发现类似TATA盒的序列。在HepG2细胞中对CYP7B1启动子/荧光素酶报告基因构建体进行的瞬时转染分析表明，该启动子具有高活性。从nt -83到+189的5'上游区域是该基因的核心启动子。
