慢性扑米酮治疗对大鼠叶酸依赖性一碳代谢的影响。

Effect of chronic primidone treatment on folate-dependent one-carbon metabolism in the rat.

作者信息

Carl G F, Gill M W, Schatz R A

出版信息

Biochem Pharmacol. 1987 Jul 1;36(13):2139-44. doi: 10.1016/0006-2952(87)90142-0.

Abstract

Rats were treated chronically with primidone (100 mg/kg/12 hr, p.o.) for up to 8 weeks. The effects of this treatment on one-carbon metabolism were determined in brain and liver. Serine hydroxymethyltransferase activity increased in both brain (44%) and liver (50%). Methylenetetrahydrofolate reductase activity increased in liver (26%) with a significant correlation to the length of treatment, but in brain it was unchanged. Methyltetrahydrofolate:homocysteine methyltransferase activity increased in brain (43%) with a significant correlation to length of treatment, but in liver no effect was observed. Methionine adenosyltransferase activity in brain was significantly lower than control at only one point after 8 weeks of chronic treatment. S-Adenosylmethionine concentration in liver increased gradually (23%) during treatment. S-Adenosylhomocysteine concentrations decreased in brain (33%) and increased in liver (23%) with chronic primidone treatment. These data support the hypothesis that chronic primidone treatment leads to folate depletion through interference with folate metabolism.

摘要

大鼠连续8周口服扑米酮（100mg/kg/12小时）进行长期治疗。测定该治疗对大脑和肝脏一碳代谢的影响。丝氨酸羟甲基转移酶活性在大脑（增加44%）和肝脏（增加50%）中均升高。亚甲基四氢叶酸还原酶活性在肝脏中升高（26%），且与治疗时长显著相关，但在大脑中无变化。甲基四氢叶酸：同型半胱氨酸甲基转移酶活性在大脑中升高（43%），且与治疗时长显著相关，但在肝脏中未观察到影响。慢性治疗8周后，仅在一个时间点大脑中的蛋氨酸腺苷转移酶活性显著低于对照组。治疗期间肝脏中S-腺苷甲硫氨酸浓度逐渐升高（23%）。慢性扑米酮治疗后，大脑中S-腺苷同型半胱氨酸浓度降低（33%），肝脏中升高（23%）。这些数据支持以下假设：慢性扑米酮治疗通过干扰叶酸代谢导致叶酸缺乏。