title: Identification of regulatory sites in the biosynthesis of ubiquinone in the perfused rat heart.
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-hydroxy[U-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-hydroxy[U-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.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Sugawara
authors.forename: K
authors.initials: K
authors.lastname: Momose
authors.forename: H
authors.initials: H
authors.lastname: Rudney
mesh_terms: D000818:Animals; D004792:Enzyme Precursors; D066298:In Vitro Techniques; D008055:Lipids / Q000096:biosynthesis; D008297:Male; D008745:Methylation; D008798:Mevalonic Acid / Q000031:analogs & derivatives; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010226:Parabens; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014451:Ubiquinone / Q000096:biosynthesis*
chemical_list: D004792:Enzyme Precursors; D008055:Lipids; D010226:Parabens; D014451:Ubiquinone; C015367:mevalonolactone; D008798:Mevalonic Acid