Nakai A, Shigematsu Y, Saito M, Kikawa Y, Sudo M
Department of Pediatrics, Fukui Medical School, Japan.
Pediatr Res. 1991 Jul;30(1):5-10. doi: 10.1203/00006450-199107000-00002.
Methylmalonate or propionate was i.v. infused into B12-deprived and control rats. In the B12-deprived rats, the plasma and liver concentrations of B12 decreased to 8 and 13%, respectively, of those of the control rats. The propionate loading produced a disproportionate increase in liver propionate levels; the mean ratio of methylmalonate to propionate in the liver was approximately 1.0 after methylmalonate loading, whereas it was 0.1 to 0.2 after propionate loading. The liver propionate and methylmalonate levels in the B12-deprived rats were twice as high as those in the control rats. The mean ratio of beta-ATP to inorganic phosphate in the liver, measured with 31P-magnetic resonance spectroscopy, decreased from 0.60 to 0.48 in the B12-deprived rats and from 0.78 to 0.63 in the control rats after methylmalonate loading; the ratio decreased from 0.57 to 0.37 in the B12-deprived rats and from 0.76 to 0.56 in the controls after propionate loading. Statistical analysis showed that propionate loading caused a more marked decrease in ATP than did methylmalonate loading (F = 26.33, degree of freedom 1 and 15; p less than 0.001), while B12-deprivation caused a more marked decrease in ATP than did the control diet (F = 92.26, df 1 and 15; p less than 0.001). The concentrations of tricarboxylic acid cycle intermediates and related organic acids in the livers of the rats suggested that propionate inhibited NAD(+)-dependent enzymes in the cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
将丙二酸单酰或丙酸静脉注射到维生素B12缺乏的大鼠和对照大鼠体内。在维生素B12缺乏的大鼠中，血浆和肝脏中维生素B12的浓度分别降至对照大鼠的8%和13%。注入丙酸后，肝脏中丙酸水平出现不成比例的升高；注入丙二酸单酰后，肝脏中丙二酸单酰与丙酸的平均比率约为1.0，而注入丙酸后该比率为0.1至0.2。维生素B12缺乏的大鼠肝脏中丙酸和丙二酸单酰水平是对照大鼠的两倍。用31P磁共振波谱法测量，注入丙二酸单酰后，维生素B12缺乏的大鼠肝脏中β-ATP与无机磷酸盐的平均比率从0.60降至0.48，对照大鼠从0.78降至0.63；注入丙酸后，维生素B12缺乏的大鼠该比率从0.57降至0.37，对照大鼠从0.76降至0.56。统计分析表明，注入丙酸比注入丙二酸单酰导致ATP更显著下降（F = 26.33，自由度1和15；p < 0.001），而维生素B12缺乏比对照饮食导致ATP更显著下降（F = 92.26，自由度1和15；p < 0.001）。大鼠肝脏中三羧酸循环中间体和相关有机酸的浓度表明，丙酸抑制了该循环中依赖NAD(+)的酶。（摘要截短至250字）
