The DOI matches its Crossref record; 41 of the 51 references it cites were found in a registry or an index.
Multiple forms of human P450 expressed in Saccharomyces cerevisiae
Abstract
We systematically characterized the levels and substrate specificity of P450s from humans and rats to extrapolate drug metabolism data from experimental animals to humans. Human P450s (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C18, 2D6, 2E1, and 3A4) were expressed in Saccharomyces cerevisiae and purified. Rat P450s were purified from hepatic microsomes of rats. We investigated the catalytic activities of purified P450s in a reconstituted system. Human CYP2B6 and rat CYP2B1 had high lidocaine N-deethylation activity. Human and rat CYP2D forms had high debrisoquine 4-hydroxylation activity. Human CYP3A4 and rat CYP3A2 had high testosterone 2 beta- and 6 beta-hydroxylation activities in a modified reconstituted system with a lipid mixture. The hydroxylation site of testosterone by CYP2B6 (16 alpha- and 16 beta-positions) agreed with that by rat CYP2B1. Human CYP2E1 had the highest lauric acid (omega-1)-hydroxylation activity and also had catalytic properties similar to those of rat CYP2E1. Human CYP2A and 2C forms had catalytic properties in testosterone metabolism different from those of rats. Antibodies raised against purified P450s were used to measure the levels of hepatic P450s. The level of CYP3A4 was the highest in human hepatic microsomes, comprising 30-40% of the total P450. CYP2C9 comprised 10-20% of the total. The levels of CYP1A2, 2A6, 2C8, 2D6, and 2E1 were moderate (5-15% of total P450). CYP2B6 content was very low. The information of this study is useful for drug metabolism and toxicological studies.
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“makes the major contribution to steroid metabolism.”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [121]
In the citing paper
“CYP3A4 is the most abundant CYP expressed in the adult liver [121,122]”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [121]
Citations
Cites
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Characterization of the common genetic defect in humans deficient in debrisoquine metabolism
Gonzalez, F. J., Skodat, R. C., Kimura, S., Umeno, M., Zanger, U. M., Nebert, D. W., Gelboin, H. V., Hardwick, J. P., & Meyer, U. (1988) · Nature · doi:10.1038/331442a0 · Cited by 715
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Kimura, S., Umeno, M., Skoda, R. C., Meyer, U., & Gonzalez, F. J. (1989) · Europe PMC (PubMed Central) · Cited by 404
The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes
Yamano, S., Tatsuno, J., & Gonzalez, F. J. (1990) · Biochemistry · doi:10.1021/bi00457a031 · Cited by 384
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Hardwick, J. P., Song, B. J., Huberman, E., & Gonzalez, F. J. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)75857-8 · Cited by 312
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Hashida, H., Kurawaka, M., Tatehana, H., Arita, A., SASAKI, N., SHIMURA, F., & YAMAZAKI, Y. (2023) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.69.206
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What We Learned from Studies on the Metabolism of Sesamin and Vitamin D
Sakaki, T., Kise, S., & Yasuda, K. (2026) · Springer eBooks · doi:10.1007/978-981-95-7068-3_5
Self-citationKamiyoshihara, I., Nakano, M., Yokoseki, I., Tomii, M., Higuchi, Y., Uehara, S., Yoneda, N., Suemizu, H., Fukami, T., & Nakajima, M. (2026) · Drug Metabolism and Disposition · doi:10.1016/j.dmd.2026.100387
Metadata
- Authors
- Imaoka, S., Yamada, T., Hiroi, T., Hayashi, K., Sakaki, T., Yabusaki, Y., & Funae, Y.
- Affiliations
- Osaka City University (JP)
- Sumitomo Chemical (Japan) (JP)
- Corresponding author
- Imaoka, Susumu
- Venue
- Biochemical Pharmacology
- Publisher
- Elsevier BV
- Published
- 1996-04
- Volume
- 51
- Issue
- 8
- Pages
- 1041-1050
- ISSN
- 0006-2952 (ISSN-L)
- OpenAlex
- W37725492
- Cited by
- 207
- References
- 51
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 3 · 2016: 9 · 2015: 7 · 2014: 7 · 2013: 2 · 2012: 8
- FWCI
- 12.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- cytochrome P450, CYP3A4, CYP2B6, CYP2D6, CYP2E1, CYP2C9, CYP2A6, CYP2C8, CYP1A2, CYP2B1, CYP3A2, CYP2C
- MeSH terms
- Animals, Antibodies, Base Sequence, Cytochrome P-450 Enzyme System, Humans, Immunoassay, Isoenzymes, Microsomes, Liver, Molecular Sequence Data, Recombinant Proteins, Saccharomyces cerevisiae, Species Specificity, Substrate Specificity, Immunoblotting, Gene Expression, Rats
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