P-450 HFLa, a form of cytochrome P-450 purified from human fetal livers, is the 16 alpha-hydroxylase of dehydroepiandrosterone 3-sulfate

• Published in: The Journal of biological chemistry Vol. 262; no. 28; pp. 13534 - 13537
• Main Authors: Kitada, M, Kamataki, T, Itahashi, K, Rikihisa, T, Kanakubo, Y
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.10.1987; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Antigen-Antibody Complex; Aryl Hydrocarbon Hydroxylases; Cytochrome b Group - metabolism; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System - metabolism; cytochrome P450; Cytochrome P450 Family 2; Cytochromes b5; dehydroepiandrosterone 3-sulfate; Fetus; Gas Chromatography-Mass Spectrometry; Humans; Immunoglobulin G; Kinetics; liver; Liver - embryology; Liver - enzymology; man; Steroid 16-alpha-Hydroxylase
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(19)76460-6

In a reconstituted system containing NADPH, dilauroyl-L-3-phosphatidylcholine, and NADPH-cytochrome P-450 reductase purified from rat liver microsomes, cytochrome P-450 (P-450 HFLa) purified from human fetal livers catalyzed the 16 alpha-hydroxylation of dehydroepiandrosterone 3-sulfate (DHEA-sulfate). Addition of cytochrome b5 purified from rat liver microsomes to the reconstituted system resulted in a remarkable increase in the hydroxylase activity. The level of P-450 HFLa in liver homogenates from human fetuses highly correlated with the activity of DHEA-sulfate 16 alpha-hydroxylase. Antibodies to P-450 HFLa inhibited the 16 alpha-hydroxylation of DHEA-sulfate in a dose-dependent manner. The NH2-terminal amino acid sequence of P-450 HFLa was similar to that of P-450NF (Beaune, P. H., Umbenhauer, D. R., Bork, R. W., Lloyd, R. S., and Guengerich, F. P. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 8064-8068). We conclude that P-450 HFLa is a form of cytochrome P-450 involved in the 16 alpha-hydroxylation of DHEA-sulfate.