Thompson G N, Walter J H, Bresson J L, Ford G C, Bonnefont J P, Chalmers R A, Saudubray J M, Leonard J V, Halliday D
Nutrition Research Group, Clinical Research Centre, Harrow, United Kingdom.
J Pediatr. 1989 Nov;115(5 Pt 1):735-9. doi: 10.1016/s0022-3476(89)80651-1.
The relative importance of endogenous metabolism and urinary metabolite excretion was assessed in vivo in six children with methylmalonic acidemia by examining the kinetics of the immediate precursor to methylmalonate, propionate. Total production and oxidation of propionate were measured by means of a continuous infusion of (1-13C)propionate and were compared with the urinary excretion of propionate metabolites. Propionate oxidation was substantial (mean 48.9 mumol/kg/hr +/- SD 18.0) and, in four children, exceeded urinary metabolite excretion (mean urinary excretion in all subjects 40 mumol/kg/hr +/- 25). The sum of urinary excretion and oxidation rates (88 mumol/kg/hr +/- 29) approximated the total propionate production (93.4 +/- 37.0), suggesting that these routes together constitute the major mechanisms of propionate disposal. These results suggest that propionate oxidation is an important route of disposal in methylmalonic acidemia. Variations in the relative proportions of propionate disposal through oxidation and urinary excretion may be one reason for the often poor correlation between clinical status and urinary metabolite excretion. Measurement of urinary metabolite concentration alone may not always reflect clinical status and responses to treatment accurately.
通过检测丙酸盐（甲基丙二酸的直接前体）的动力学，在六名甲基丙二酸血症患儿体内评估了内源性代谢和尿代谢产物排泄的相对重要性。通过持续输注(1-¹³C)丙酸盐来测量丙酸盐的总生成量和氧化量，并与丙酸盐代谢产物的尿排泄量进行比较。丙酸盐氧化量可观（平均48.9 μmol/kg/小时±标准差18.0），在四名患儿中，丙酸盐氧化量超过了尿代谢产物排泄量（所有受试者的平均尿排泄量为40 μmol/kg/小时±25）。尿排泄率和氧化率之和（88 μmol/kg/小时±29）接近丙酸盐总生成量（93.4±37.0），这表明这些途径共同构成了丙酸盐清除的主要机制。这些结果表明，丙酸盐氧化是甲基丙二酸血症中重要的清除途径。通过氧化和尿排泄进行的丙酸盐清除相对比例的变化，可能是临床状态与尿代谢产物排泄之间常常缺乏良好相关性的一个原因。仅测量尿代谢产物浓度可能并不总能准确反映临床状态和对治疗的反应。
