Camiña F, Novo-Rodriguez M I, Rodriguez-Segade S, Castro-Gago M
Departamento de Bioquímica, Hospital General de Galicia, Spain.
Clin Chim Acta. 1995 Dec 29;243(2):151-64. doi: 10.1016/0009-8981(95)06164-9.
We determined levels of purines, purine metabolites, related enzymes and carnitine in muscle of 8 untreated Duchenne muscular dystrophy (DMD) patients, 12 allopurinol-treated DMD patients and 12 age-matched controls. Muscle of DMD patients was found to be deficient in ATP, ADP, adenylsuccinate, hypoxanthine, guanine and adenylsuccinate synthetase. In allopurinol-treated DMD patients, mean total adenylate level was only three times less than in controls (versus 14 times less in untreated DMD patients). Mean inosine monophosphate (IMP), adenine, adenosine, inosine, xanthine, guanine, guanosine and uric acid levels were higher in allopurinol-treated patients than in controls, while mean adenylsuccinate levels were higher than in untreated patients. Allopurinol also restored acylcarnitine levels to normal and significantly increased free carnitine levels. These findings strongly support the hypothesis that Duchenne muscular dystrophy involves alterations leading to blockage of the IMP-->purine pathway and that allopurinol treatment favours restoration of purine levels by this route. Furthermore, our results suggest that the observed deficiencies in cell components unrelated to purine metabolism are long-term secondary effects.
我们测定了8名未经治疗的杜兴氏肌营养不良症（DMD）患者、12名接受别嘌呤醇治疗的DMD患者以及12名年龄匹配的对照组患者肌肉中的嘌呤、嘌呤代谢产物、相关酶和肉碱水平。发现DMD患者的肌肉中ATP、ADP、腺苷酸琥珀酸、次黄嘌呤、鸟嘌呤和腺苷酸琥珀酸合成酶缺乏。在接受别嘌呤醇治疗的DMD患者中，平均总腺苷酸水平仅比对照组低三倍（而未经治疗的DMD患者低14倍）。接受别嘌呤醇治疗的患者中，平均肌苷单磷酸（IMP）、腺嘌呤、腺苷、肌苷、黄嘌呤、鸟嘌呤、鸟苷和尿酸水平高于对照组，而平均腺苷酸琥珀酸水平高于未经治疗的患者。别嘌呤醇还使酰基肉碱水平恢复正常，并显著提高了游离肉碱水平。这些发现有力地支持了以下假设：杜兴氏肌营养不良症涉及导致IMP→嘌呤途径受阻的改变，且别嘌呤醇治疗有利于通过该途径恢复嘌呤水平。此外，我们的结果表明，观察到的与嘌呤代谢无关的细胞成分缺乏是长期的继发效应。
