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Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism.
Kawainoto T,
Mitsuuchi Y,
Ohnishi T,
Ichikawa Y,
Yokoyama Y,
Sumimoto H,
Toda K,
Miyahara K,
Kuribayashi I,
Nakao K, et al.
Department of Medical Chemistry, Kochi Medical School, Japan.
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.
PMID: 2256920 [PubMed - indexed for MEDLINE]
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Cited by 6 PubMed Central articles
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Mutations in the CYP11B1 gene causing congenital adrenal hyperplasia and hypertension cluster in exons 6, 7, and 8.
Curnow KM, Slutsker L, Vitek J, Cole T, Speiser PW, New MI, White PC, Pascoe L.
Proc Natl Acad Sci U S A. 1993 May 15; 90(10):4552-6.
[Proc Natl Acad Sci U S A. 1993]
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ReviewGenetic determinants of human hypertension.
Lifton RP.
Proc Natl Acad Sci U S A. 1995 Sep 12; 92(19):8545-51.
[Proc Natl Acad Sci U S A. 1995]
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Mutation T318M in the CYP11B2 gene encoding P450c11AS (aldosterone synthase) causes corticosterone methyl oxidase II deficiency.
Zhang G, Rodriguez H, Fardella CE, Harris DA, Miller WL.
Am J Hum Genet. 1995 Nov; 57(5):1037-43.
[Am J Hum Genet. 1995]
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