Cited by 153Hormonal Regulation and HypertensionAdrenal Hormones and DisordersSteroid Chemistry and Biochemistry

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Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism

Kawamoto, Takeshi, Mitsuuchi, Yasuhiro, Ohnishi, Taira, Ichikawa, Yoshiyuki, Yokoyama, Yuichi, Sumimoto, Hidetoshi, Toda, Katsumi, Miyahara, Kaoru, Kuribayashi, Isao, Nakao, Kazuwa, Hosoda, Kiminori, Yamamoto, Yasutake, Imura, Hiroo, Shizuta, Yutaka·1990·Biochemical and Biophysical Research Communications

DOI 10.1016/s0006-291x(05)81058-7

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Abstract

A cDNA clone encoding human aldosterone synthase cytochrome P-450 (P-450aldo) has been isolated from a cDNA library derived from human adrenal tumor of a patient suffering from primary aldosteronism. The insert of the clone contains an open reading frame encoding a protein of 503 amino acid residues together with a 3 bp 5'-untranslated region and a 1424 bp 3'-untranslated region to which a poly(A) tract is attached. The nucleotide sequence of P-450aldo cDNA is 93% identical to that of P-450(11) beta cDNA. Catalytic functions of these two P-450s expressed in COS-7 cells are very similar in that both enzymes catalyze the formation of corticosterone and 18-hydroxy-11-deoxycorticosterone using 11-deoxycorticosterone as a substrate. However, they are distinctly different from each other in that P-450aldo preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone while P-450(11)beta substantially fails to catalyze the reaction to form aldosterone. These results suggest that P-450aldo is a variant of P-450(11)beta, but this enzyme is a different gene product possibly playing a major role in the synthesis of aldosterone at least in a patient suffering from primary aldosteronism.

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Self-citation
Defects of Adrenal Steroidogenesis
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Molecular identity and gene expression of aldosterone synthase cytochrome P450
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Authors: Kawamoto, T., Mitsuuchi, Y., Ohnishi, T., Ichikawa, Y., Yokoyama, Y., Sumimoto, H., Toda, K., Miyahara, K., Kuribayashi, I., Nakao, K., Hosoda, K., Yamamoto, Y., Imura, H., & Shizuta, Y.
Affiliations: Kochi Medical School Hospital (JP)
Kyoto University (JP)
Kagawa University (JP)
ORCID: Kawamoto, Takeshi
Yokoyama, Yuichi
Nakao, Kazuwa
Hosoda, Kiminori
Venue: Biochemical and Biophysical Research Communications
Publisher: Elsevier BV
Published: 1990-11
Volume: 173
Issue: 1
Pages: 309-316
ISSN: 0006-291X (ISSN-L)
DOI: 10.1016/s0006-291x(05)81058-7
OpenAlex: W1990953561
Cited by: 152
References: 26
Citations by year: 2023: 1 · 2022: 1 · 2019: 1 · 2018: 2 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 4 · 2012: 2
FWCI: 12.27
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Biochemical and Biophysical Research Communications (publishedVersion)
PubMed (publishedVersion)
Funders: Ministry of Education, Culture, Sports, Science and Technology
Korea Toray Science Foundation
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
Keywords: aldosterone synthase, primary aldosteronism, cDNA cloning, adrenal tumors, aldosterone biosynthesis, deoxycorticosterone, corticosterone, 18-hydroxy-11-deoxycorticosterone
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cloning, Molecular, Cytochrome P-450 Enzyme System, DNA, Humans, Hyperaldosteronism, Mitochondria, Molecular Sequence Data, Recombinant Proteins, Steroid Hydroxylases, Substrate Specificity, Transfection, Restriction Mapping, Oligonucleotide Probes, Gene Expression, Cytochrome P-450 CYP11B2

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Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism

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