Saada Ann, Bar-Meir Maskit, Belaiche Corinne, Miller Chaya, Elpeleg Orly
Metabolic Disease Unit, Shaare-Zedek Medical Center, POB 3235, Jerusalem 91031, Israel.
Anal Biochem. 2004 Dec 1;335(1):66-72. doi: 10.1016/j.ab.2004.08.015.
Isolated complex I deficiency is the most common oxidative phosphorylation defect and is associated with substantial morbidity and mortality. The diagnosis is made by enzymatic analysis and for most patients the molecular pathology remains undefined. Various cofactors and vitamins are frequently administered, but their efficacy have been difficult to assess. We employed determination of ATP production in fibroblast cell lines from patients with complex I deficiency to evaluate the usefulness of therapeutic agents. The effect of each additive varied among the different patients with certain agents favorably affecting ATP production rate in some of the patients and adversely affecting it in others. The reduced nicotinamide adenine dinucleotide (NADH)-ferricyanide reductase assay in muscle mitochondria correlated better than the NADH-coenzyme Q and NADH-cytochrome c assays with ATP production rate in fibroblasts. Our results underscore the necessity of evaluation of different agents for each patient separately. The NADH-ferricyanide reductase assay play a helpful role in directing mutation analysis and identifying patients which are more likely to have their cells amenable for ATP production assessment.
孤立性复合物I缺乏是最常见的氧化磷酸化缺陷，与相当高的发病率和死亡率相关。诊断通过酶分析进行，对于大多数患者而言，分子病理学仍不明确。经常给予各种辅助因子和维生素，但其疗效难以评估。我们通过测定复合物I缺乏患者成纤维细胞系中的ATP生成，来评估治疗药物的效用。每种添加剂的效果在不同患者中各不相同，某些药物对一些患者的ATP生成速率有有利影响，而对另一些患者则有不利影响。肌肉线粒体中的还原型烟酰胺腺嘌呤二核苷酸（NADH）-铁氰化物还原酶测定与成纤维细胞中的ATP生成速率的相关性，优于NADH-辅酶Q和NADH-细胞色素c测定。我们的结果强调了针对每位患者分别评估不同药物的必要性。NADH-铁氰化物还原酶测定在指导突变分析和识别其细胞更有可能适用于ATP生成评估的患者方面发挥了有益作用。
