Identification of regulatory sites in the biosynthesis of ubiquinone in the perfused rat heart |
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Authors: | T Yamamoto S Shimizu H Sugawara K Momose H Rudney |
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Institution: | Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan. |
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Abstract: | The biosynthesis of ubiquinone was studied in an isolated perfused beating heart preparation from adult male rats to determine rate-limiting steps in the biosynthetic pathway. The isolated heart could incorporate p-hydroxyU-14C]benzoate into ubiquinones (ubiquinone-9 and -10) and two other lipids which were identified as 3-nonaprenyl 4-hydroxybenzoate and 3-decaprenyl 4-hydroxybenzoate. No other lipids could be detected. Addition of unlabeled mevalonolactone to the perfusate stimulated the rate of incorporation of p-hydroxyU-14C]benzoate into 3-nonaprenyl 4-hydroxybenzoate and 3-decaprenyl 4-hydroxybenzoate. The level of radioactivity in these intermediates was much greater than that in ubiquinone-9 and -10. These results show that in the intact heart there is a large excess capacity to form postmevalonate isoprenoid precursors of ubiquinone and suggest a possible regulatory step at the premevalonate level. Moreover, the accumulation of prenylated derivatives of 4-hydroxybenzoic acid indicates further rate limitation at one or more of the subsequent steps in conversion of these intermediates to ubiquinone. |
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