ATP-Dependent Transport of Bile Acid Intermediates across Rat Liver Peroxisomal Membranes
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概要
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The bile acid intermediate 3α, 7α, 12α-trihydroxy-5β-cholestanoic acid (THCA) is converted to cholic acid exclusively in peroxisomes by the oxidative cleavage of the side chain. To investigate the mechanism by which the biosynthetic intermediates of bile acids are transported into peroxisomes, we incubated THCA or its CoA ester (THC-CoA) with isolated intact rat liver peroxisomes and analyzed their oxidation products, cholic acid and 3α, 7α, 12α-trihydroxy-5β-cholest-24-enoic acid. The oxidation of both THCA and THC-CoA was dependent on incubation time and peroxisomal proteins, and was stimulated by ATP. THC-CoA was efficiently oxidized to cholic acid and 3α, 7α, 12α-trihydroxy-50-cholest-24-enoic acid as compared with THCA, suggesting that THC-CoA is the preferred substrate for transport into peroxisomes. The oxidation of THC-CoA was significantly inhibited by sodium azide, verapamile, and N-ethylmaleimide. Furthermore, the stimulatory effect of ATP on the oxidation was not replaced by GTP or AMP. In addition, the ATP-dependent oxidation of THC-CoA was markedly inhibited by pretreatment of peroxisomes with proteinase K when peroxi-somal matrix proteins were not degraded. These results suggest that an ATP-dependent transport system for THC-CoA exists on peroxisomal membranes.
- 社団法人 日本生化学会の論文
著者
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Une Mizuho
Division Of Medical Chemistry Programs For Pharmaceutical Sciences Graduate School Of Biomedical Sci
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Imanaka Tsuneo
Department Of Biological Chemistry Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceuti
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Iguchi Yusuke
Division Of Medical Chemistry Programs For Pharmaceutical Sciences Graduate School Of Biomedical Sci
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Sakamoto Tomoko
Division Of Medical Chemistry Programs For Pharmaceutical Sciences Graduate School Of Biomedical Sci
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Morita Masashi
Department Of Biological Chemistry Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceuti
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Suzuki Yasuyuki
Department Of Anesthesia And Icu National Children's Hospital
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Iguchi Yusuke
Division of Medical Chemistry, Programs for Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University
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Morita Masashi
Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
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Tomita Takashi
Division of Clinical Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Hiroshima University
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