The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism
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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“Two isoforms of CYP11B are expressed in the zona glomerulosa, both with the ability to catalyze the 11β-hydroxylation of DOC yielding corticosterone.”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [29]
In the citing paper
“CYP11B2, which is also known as aldosterone synthase, additionally exhibits 18-hydroxylase and 18-methyl oxidase activity, which are required to convert corticosterone to aldosterone via the 18-hydroxycorticosterone intermediate [26,28,29].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [29]
Citations
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Nelson, D. R., Kamataki, T., Waxman, D. J., Guengerich, F. P., Estabrook, R. W., Feyereisen, R., Gonzalez, F. J., Coon, M. J., GUNSALUS, I. C., Gotoh, O., et al. (1993) · DNA and Cell Biology · doi:10.1089/dna.1993.12.1 · Cited by 1,647
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Molecular Genetics of Human Blood Pressure Variation
Lifton, R. P. (1996) · Science · doi:10.1126/science.272.5262.676 · Cited by 623
Steroidogenic enzymes: Structure, function, and role in regulation of steroid hormone biosynthesis
Hanukoglu, I. (1992) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(92)90307-5 · Cited by 577
Metadata
- 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)
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 1990-11
- Volume
- 173
- Issue
- 1
- Pages
- 309-316
- ISSN
- 0006-291X (ISSN-L)
- 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
- 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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