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Action of different nucleotides on the last step of aldosterone synthesis
Authors:B Aupetit  N Emeric  C Accarie  V Vonarx
Institution:1. Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK;2. MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK;3. Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK;1. Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China;2. National Clinical Research Center for Skin and Immune Diseases, Beijing, China;3. Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China;4. National Medical Products Administration Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, China;1. Department of Neurology, The First Hospital of Shanxi Medical University, Taiyuan, 030001, China;2. Department of Geriatrics, General Hospital of TISCO, Taiyuan, 030001, China;3. General Hospital of TISCO, Taiyuan, 030001, China;1. Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York;2. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Abstract:The effect of various nucleotides on the last step of aldosterone biosynthesis, the so-called "18 oxidation" (transformation of 18-hydroxycorticosterone to aldosterone), was studied by incubation of tritiated 18-hydroxycorticosterone with untreated duck adrenal mitochondria in vitro. The study was carried out in the absence or in the presence of antimycin A which blocks the respiratory chain. Results show that, when oxidative phosphorylation chain functions normally, GTP and CTP had no effect, UTP stimulated this reaction but ADP and ATP inhibited the transformation of 18-hydroxycorticosterone into aldosterone to the same extent. For this reason ATP is included in all controls for experiments studying the effect of ATP when "18 oxidation" is inhibited by antimycin A. When oxidative phosphorylation chain is inhibited by antimycin A, ATP is able to reverse the inhibition of "18 oxidation" induced by antimycin A, in the presence of succinate. Under these conditions UTP is not able to reverse the inhibition induced by antimycin A; GTP and CTP had no effect. Effects of ATP and UTP on the last step of aldosterone biosynthesis are related to different mechanisms. ATP clearly acts as an energy source for "18 oxidation" in the presence of succinate. The role of UTP must still be determined.
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