Yamamoto T, Shimizu S, Sugawara H, Momose K, Rudney H
Department of Pharmacology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Arch Biochem Biophys. 1989 Feb 15;269(1):86-92. doi: 10.1016/0003-9861(89)90089-1.
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.
在成年雄性大鼠的离体灌注搏动心脏标本中研究了泛醌的生物合成，以确定生物合成途径中的限速步骤。离体心脏可将对羟基[U-¹⁴C]苯甲酸掺入泛醌（泛醌-9和-10）以及另外两种脂质中，这两种脂质被鉴定为3-壬异戊二烯基4-羟基苯甲酸酯和3-癸异戊二烯基4-羟基苯甲酸酯。未检测到其他脂质。向灌注液中添加未标记的甲羟戊酸内酯可刺激对羟基[U-¹⁴C]苯甲酸掺入3-壬异戊二烯基4-羟基苯甲酸酯和3-癸异戊二烯基4-羟基苯甲酸酯的速率。这些中间体中的放射性水平远高于泛醌-9和-10中的放射性水平。这些结果表明，在完整心脏中，形成泛醌的甲羟戊酸后类异戊二烯前体的能力有大量过剩，并提示在甲羟戊酸前水平可能存在一个调节步骤。此外，4-羟基苯甲酸的异戊二烯化衍生物的积累表明，在这些中间体转化为泛醌的后续一个或多个步骤中存在进一步的速率限制。
