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.

1)我们开发了一种新的有机酸-葡萄糖醛酸酯（d-葡萄糖醛酸-1-0-酰基衍生物）的合成方法，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)酰基肉碱的自动定量分析方法是基于使用具有柱切换的羧酸分析仪。去除颗粒物后，直接定量尿中短链酰基肉碱。从尿液取样到同时计算酰基肉碱的总分析时间为120分钟。酰基肉碱的检出限为50p mol。由于采用了新型羧酸分析仪（S-3000型，10p mol），具有较高的灵敏度。3)甲基丙二酸尿患者的尿液和羊水中甲基丙二酸肉碱含量极低，但这些患者的组织中甲基丙二酸肉碱含量显著。4)虽然在研究期间头孢特仑酯治疗患者血清游离肉碱水平显著降低，但患者的临床状态及血氨、乳酸、丙酮酸水平无明显变化。未发现线粒体功能障碍。液相色谱/质谱法检测血清中有机酸-葡萄糖醛酸酯和γ -丁糖苷的灵敏度不足。为此，需要使用高灵敏度的羧酸分析仪进行进一步的研究。

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.