Barshop B A, Yoshida I, Ajami A, Sweetman L, Wolff J A, Sweetman F R, Prodanos C, Smith M, Nyhan W L
Department of Pediatrics, University of California San Diego, La Jolla 92093.
Pediatr Res. 1991 Jul;30(1):15-22. doi: 10.1203/00006450-199107000-00004.
Metabolism of propionate in human subjects was studied using bolus administration of 1-13C-propionate i.v. or orally. The study population consisted of five patients with propionic acidemia (PA), eight with methylmalonic acidemia (MMA; four responsive to vitamin B12), one each with multiple carboxylase deficiency and transcobalamin-II deficiency, and five healthy volunteers. Concentrations of 1-13C-propionate were measured in blood in three patients with PA, two with MMA, and two controls. Breath samples were obtained at intervals during 3 h after the dose, isotopic enrichment of 13CO2 was measured, and the cumulative percentage of recovery of 13C was calculated from the individual's predicted resting energy expenditure. Recovery of 13CO2 and half-time of 1-13C-propionate in PA were significantly less than normal. The same parameters in MMA were below normal, but significantly greater than in PA. Recovery of 13CO2 was well correlated with clinical severity in PA, but did not correlate in MMA. Differences between MMA and PA may indicate different distribution of propionate pools, differences in inducibility of residual enzyme activities, or an alternate pathway for decarboxylation of propionate available in MMA but not PA. Only one patient with PA demonstrated increased 13CO2 production during biotin treatment. In a B12-responsive MMA patient, no differences were noted within 2 d of initiating treatment with B12, but there was an increase in 13CO2 production after 4 mo. Recovery of 13CO2 was normal in the patient with transcobalamin-II deficiency before and after treatment with vitamin B12.(ABSTRACT TRUNCATED AT 250 WORDS)
通过静脉内或口服给予1-13C-丙酸盐推注，对人体受试者丙酸盐的代谢进行了研究。研究人群包括5例丙酸血症（PA）患者、8例甲基丙二酸血症（MMA；4例对维生素B12有反应）患者、1例多种羧化酶缺乏症患者和1例转钴胺素II缺乏症患者，以及5名健康志愿者。对3例PA患者、2例MMA患者和2名对照者的血液中1-13C-丙酸盐浓度进行了测量。在给药后3小时内定期采集呼气样本，测量13CO2的同位素富集度，并根据个体预测的静息能量消耗计算13C的累积回收率。PA患者中13CO2的回收率和1-13C-丙酸盐的半衰期显著低于正常水平。MMA患者的相同参数低于正常水平，但显著高于PA患者。PA患者中13CO2的回收率与临床严重程度密切相关，但在MMA患者中无相关性。MMA和PA之间的差异可能表明丙酸盐池的分布不同、残余酶活性的诱导性差异，或MMA中存在但PA中不存在的丙酸盐脱羧替代途径。只有1例PA患者在生物素治疗期间表现出13CO2产生增加。在1例对维生素B12有反应的MMA患者中，开始使用维生素B12治疗后2天内未观察到差异，但4个月后13CO2产生增加。转钴胺素II缺乏症患者在维生素B12治疗前后13CO2的回收率均正常。（摘要截短至250字）
