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Research of diagnosis and therapy for inborn error of organic acid metabolism: Analysis of acylcarnitines and organic acid-glucuronides, and their appreciations for diagnosis and therapy.

先天性有机酸代谢缺陷的诊断和治疗研究：酰基肉碱和有机酸葡萄糖苷酸的分析及其对诊断和治疗的评价。

基本信息

批准号：
03454267
负责人：
WADA Yoshiro
金额：
$ 2.56万
依托单位：
Nagoya City University Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

1) We have developed a new synthesis mehtod of organic acid-glucuronides (D-glucuronic acid-1-0-Acyl derivatives), which will contribute to the study of organic acid metabolism as well as to that of drug metabolism and detoxification.2) The automatic quantitative analytical method for acylcarnitines is based on the use of a carboxilic acid analyzer with column switching. With removed particulate matter, urinary short-medium chain acylcarnitines were directly quantified. Total analysis time from urine sampling to the simultaneous calculation of the acylcarnitines is 120 min. Detection limits of the acylcarnitines were 50p mol. The high sensitivity was possible due to the use of a new carboxylic acid analyzer(S-3000 type; 10p mol).3) The presence of methylmalonylcarnitine was minimal in urine and amniotic fluid in patients with methylmalonic aciduria, although significant levels were observed in tissues of these patients.4) Although serum free carnitine in patients with cefteram pivoxil medication was dramatically decreased during the study period,these patients' clinical state, and blood ammonia, lactate and pyruvate levels were not significantly change. Mitochondrial dysfunction was not suggested.The sensitivity of LC/MS was insufficient for detection of organic acid-glucuronides and gamma-butyrobetain in serums. For this, further study will be required using a high sensitive carboxylic acid analyzer.

1）我们开发了有机酸-葡萄糖醛酸（D-葡萄糖醛酸-1-0-酰基衍生物）的新合成方法，这将有助于有机酸代谢的研究以及药物代谢和解毒的研究。2）基于使用柱切换的羧酸分析仪的酰基肉碱自动定量分析方法。去除颗粒物后，直接对尿中短链酰基肉碱进行定量。从尿液取样到同时计算酰基肉碱的总分析时间为 120 分钟。酰基肉碱的检测限为 50p mol。由于使用了新型羧酸分析仪（S-3000 型；10p mol），因此实现了高灵敏度。3) 尽管在甲基丙二酸尿症患者的尿液和羊水中观察到了显着水平的甲基丙二酰肉碱，但在这些患者的组织中观察到了显着水平的甲基丙二酰肉碱。4) 尽管使用头孢特仑匹酯治疗的患者中血清游离肉碱显着降低研究期间，这些患者的临床状态以及血氨、乳酸和丙酮酸水平均无显着变化。未提示线粒体功能障碍。LC/MS 的灵敏度不足以检测血清中的有机酸-葡萄糖苷酸和γ-丁甜菜碱。为此，需要使用高灵敏度羧酸分析仪进行进一步研究。