- Inhibition of aldosterone formation by cortisol in rat adrenal mitochondria
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In this work we confirm by a metabolic method the existence of at least two enzymes with 11β- and 18-hydroxylase activities in rat adrenal mitochondria.The method was based on the ability of cortisol (F), a foreign alternative substrate, to inhibit competitively metabolite productions from various precursors.F inhibited a) aldosterone (ALDO) production from 11-deoxycorticosterone (DOC) without affecting the yields of corticosterone (B) and 18-hydroxy-11-deoxycorticosterone (18-OHDOC); b) 18-hydroxycorticosterone and aldosterone productions from B (Ki = 2.5 +/- 0.5 μM); and c) ALDO production from 18-OHDOC.These results suggest the existence of two categories of enzymes with both 11β- and 18-hydroxylase activities, one comprising those that catalyze the conversions of DOC to B and 18-OHDOC (F-insensitive reactions ) and the other one comprising the enzymes involved in the conversions of B to 18-OHB and ALDO and that of 18-OHDOC to ALDO (F-sensitive reactions ).The cloned enzymes CYP11B1 and CYP11B2 would pertain respectively to the FIS and FS categories. - Keywords: aldosterone; adrenal; cytochrome P450; 11β,18-hydroxylases; steroidogenesis; Cortisol
- Matkovic, Laura,Gomez-Sanchez, Celso E.,Lantos, Carlos P.,Cozza, Eduardo N.
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p. 447 - 452
(2007/10/02)
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- Cytotoxic nucleoside-corticosteroid phosphodiesters
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Nucleotides of nucleosides or bases having known cytotoxic activity are reacted with steroids, preferably corticosteroids, to form corresponding cytotoxic nucleoside-corticosteroid phosphodiester analogues of the formula: STR1 wherein: steroid is the residue formed by removal of a hydroxyl hydrogen atom from a natural or synthetic adrenal corticosteroid containing the characteristic cyclopentanophenanthrene nucleus which is esterified to the phosphate moiety at the 21-position; sugar is a naturally occurring pentose or deoxypentose in the furanose form, preferably ribose, deoxyribose, lyxose, xylose or arabinose and especially ribose, deoxyribose or arabinose, which is esterified to the phosphate moiety at the 5'-position and covalently bonded to the heterocycle moiety at the 1'-position to form a nucleoside; and heterocycle is a purine, pyrimidine, hydrogenated pyrimidine, triazolopurine or similar nucleoside base. The conjugates exhibit an enhanced therapeutic index as compared to the parent nucleoside or base compounds, and are thus useful cytotoxic, antiviral and antineoplastic agents.
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