Ozeir Mohammad, Mühlenhoff Ulrich, Webert Holger, Lill Roland, Fontecave Marc, Pierrel Fabien
CEA, iRTSV, Laboratoire Chimie et Biologie des Métaux, F-38054 Grenoble, France.
Chem Biol. 2011 Sep 23;18(9):1134-42. doi: 10.1016/j.chembiol.2011.07.008.
Coenzyme Q (Q), an essential component of eukaryotic cells, is synthesized by several enzymes from the precursor 4-hydroxybenzoic acid. Mutations in six of the Q biosynthesis genes cause diseases that can sometimes be ameliorated by oral Q supplementation. We establish here that Coq6, a predicted flavin-dependent monooxygenase, is involved exclusively in the C5-hydroxylation reaction. In an unusual way, the ferredoxin Yah1 and the ferredoxin reductase Arh1 may be the in vivo source of electrons for Coq6. We also show that hydroxylated analogs of 4-hydroxybenzoic acid, such as vanillic acid or 3,4-dihydroxybenzoic acid, restore Q biosynthesis and respiration in a Saccharomyces cerevisiae coq6 mutant. Our results demonstrate that appropriate analogs of 4-hydroxybenzoic acid can bypass a deficient Q biosynthetic enzyme and might be considered for the treatment of some primary Q deficiencies.
辅酶Q（Q）是真核细胞的重要组成部分，由几种酶从前体4-羟基苯甲酸合成。Q生物合成基因中的六个基因发生突变会导致疾病，有时口服补充Q可改善这些疾病。我们在此确定，Coq6是一种预测的黄素依赖性单加氧酶，专门参与C5-羟基化反应。以一种不同寻常的方式，铁氧化还原蛋白Yah1和铁氧化还原蛋白还原酶Arh1可能是Coq6在体内的电子来源。我们还表明，4-羟基苯甲酸的羟基化类似物，如香草酸或3,4-二羟基苯甲酸，可恢复酿酒酵母coq6突变体中的Q生物合成和呼吸作用。我们的结果表明，4-羟基苯甲酸的适当类似物可以绕过缺陷的Q生物合成酶，可能可用于治疗某些原发性Q缺乏症。
