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)本研究开发了一种新的有机酸-葡萄糖醛酸苷（D-葡萄糖醛酸-1-O-酰基衍生物）的合成方法，为有机酸代谢研究以及药物代谢和解毒研究提供了新的思路。2）采用柱切换羧酸分析仪，建立了酰基肉毒碱的自动定量分析方法。去除颗粒物质后，直接定量尿中短链酰基肉毒碱。总分析时间从尿液采样到同时计算的酰基肉毒碱是120分钟。检测限的酰基肉毒碱为50 μ mol。高灵敏度是可能的，由于使用了一种新的羧酸分析仪（S-3000型; 10 μ mol）。3）甲基丙二酸尿症患者的尿液和羊水中甲基丙二酸卡尼汀的存在最小，尽管在这些患者的组织中观察到显著水平。4）尽管在研究期间头孢特仑酯药物治疗的患者中血清游离卡尼汀显著降低，患者临床状态、血氨、乳酸、丙酮酸水平无明显变化。LC/MS检测血清中有机酸葡萄糖醛酸苷和γ-丁酸甜菜碱的灵敏度不足。为此，需要使用高灵敏度羧酸分析仪进行进一步研究。

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.