Marriage Barbara J, Clandinin M Thomas, Macdonald Ian M, Glerum D Moira
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Mol Genet Metab. 2004 Apr;81(4):263-72. doi: 10.1016/j.ymgme.2003.12.008.
Marked progress has been made over the past 15 years in defining the specific biochemical defects and underlying molecular mechanisms of oxidative phosphorylation disorders, but limited information is currently available on the development and evaluation of effective treatment approaches. Metabolic therapies that have been reported to produce a positive effect include coenzyme Q(10) (ubiquinone), other antioxidants such as ascorbic acid and vitamin E, riboflavin, thiamine, niacin, vitamin K (phylloquinone and menadione), and carnitine. The goal of these therapies is to increase mitochondrial ATP production, and to slow or arrest the progression of clinical symptoms. In the present study, we demonstrate for the first time that there is a significant increase in ATP synthetic capacity in lymphocytes from patients undergoing cofactor treatment. We also examined in vitro cofactor supplementation in control lymphocytes in order to determine the effect of the individual components of the cofactor treatment on ATP synthesis. A dose-dependent increase in ATP synthesis with CoQ(10) incubation was demonstrated, which supports the proposal that CoQ(10) may have a beneficial effect in the treatment of oxidative phosphorylation (OXPHOS) disorders.
在过去15年中，在确定氧化磷酸化障碍的特定生化缺陷和潜在分子机制方面取得了显著进展，但目前关于有效治疗方法的开发和评估的信息有限。据报道产生积极效果的代谢疗法包括辅酶Q(10)（泛醌）、其他抗氧化剂如抗坏血酸和维生素E、核黄素、硫胺素、烟酸、维生素K（叶绿醌和甲萘醌）以及肉碱。这些疗法的目标是增加线粒体ATP的产生，并减缓或阻止临床症状的进展。在本研究中，我们首次证明接受辅助因子治疗的患者淋巴细胞中的ATP合成能力显著增加。我们还在对照淋巴细胞中检测了体外辅助因子补充，以确定辅助因子治疗的各个成分对ATP合成的影响。结果表明，随着辅酶Q(10)孵育，ATP合成呈剂量依赖性增加，这支持了辅酶Q(10)可能对氧化磷酸化（OXPHOS）障碍的治疗具有有益作用的提议。
