Cytochrome P450(11β): Structure-function relationship of the enzyme and its involvement in blood pressure regulation

Mitsuhiro Okamoto, Yasuki Nonaka, Miho Ohta, Hiroshi Takemori, Sunil Krishna Halder, Zhi nong Wang, Tiejun Sun, Osamu Hatano, Akira Takakusu, Tetsuo Murakami

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Cytochrome P450(11β) is deeply involved in the final steps of biosynthesis of mineralocorticoids. This paper deals with following issues about this enzyme. (1) The structure and function of the enzymes of various animal species are discussed. By making alignment of amino acid sequences of the enzymes, we identified peptide domains essential for the enzyme actions such as a putative steroid binding domain and a heme binding region. Estimates of molecular similarity among the P450(11β) family enzymes suggested that the enzymes having both 11β-hydroxylation activity and aldosterone (ALDO) synthetic activity of certain animals such as frog, cattle and pig are more similar to the ALDO synthases of the other animals, such as rat, mouse and human, than the 11β-hydroxylases of these animals. (2) The molecular nature of the P450(11β) family enzymes of genetically hypertensive rats as well as adrenal regeneration hypertension (ARH) rats is examined. (i) Mutation was found in the P450(11β) gene of Dahl's salt-resistant normotensive rat. Steroidogenic activity expressed by the mutated gene accounted well for abnormal plasma levels of steroid hormones in this rat. (ii) 11β-, 18- and 19-Hydroxylation activities of adrenal mitochondria prepared from spontaneously hypertensive rat (SHR), Wistar-Kyoto rat (WKY), and stroke-prone (SP)-SHR were not significantly different from each other. Levels of mRNA of ALDO synthase in adrenal glands of 50-week-old SHR was significantly lower than those of 10-week-old SHR, WKY and SHR-SP. (iii) No significant difference in 19-hydroxylation activity was found between adrenal mitochondria prepared from ARH rat and those from control rat. The level of message of ALDO synthase was lower in adrenal glands of ARH rat.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume53
Issue number1-6
DOIs
StatePublished - Jun 1995

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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    Okamoto, M., Nonaka, Y., Ohta, M., Takemori, H., Halder, S. K., Wang, Z. N., Sun, T., Hatano, O., Takakusu, A., & Murakami, T. (1995). Cytochrome P450(11β): Structure-function relationship of the enzyme and its involvement in blood pressure regulation. Journal of Steroid Biochemistry and Molecular Biology, 53(1-6), 89-94. https://doi.org/10.1016/0960-0760(95)00025-U