Wang R S, Nakajima T
Department of Hygiene, Shinshu University School of Medicine, Matsumoto, Japan.
Arch Toxicol. 1991;65(1):39-44. doi: 10.1007/BF01973501.
In vitro metabolism of toluene was investigated at substrate concentrations of 0.03-6.25 mM in liver microsomes from control and ethanol- and phenobarbital (PB)-treated rats. Three metabolites, benzylalcohol (BA), o- and p-cresol, were measured by high-performance liquid chromatograph. BA was the main metabolite of toluene, whereas o- and p-cresol contributed only 1.1-1.5% and 1.7-2.8% of total metabolites, respectively, in microsomes from control rats. Ethanol treatment showed little effect on the percentages of three metabolites, but PB increased the percentages of o- and p-cresol to as high as 5.5% and 8.0%, respectively, following the increase in toluene concentration. There were two different isozymes with different Km involved in the side-chain hydroxylation of toluene in microsomes from control and ethanol-treated rats. One had a low Km value (0.13-0.17 mM) and could be greatly induced with ethanol treatment. The other was a high Km isozyme (0.60-0.87 mM). PB-induced isozyme showed a similar Km value to that of the high Km isozyme existing in microsomes from control and ethanol-treated rats. Two isozymes were involved in the formation of p-cresol in microsomes of control rats: the low-Km type had a similar value (0.15 mM) to the low isozyme of BA formation, but the high Km isozyme had a larger value (2.04 mM) than the high isozyme of BA. Only one enzyme responsible for o-cresol formation was detected in microsomes of control rats, and had a similar Km (2.11 mM) to that of the high Km isozyme of p-cresol.(ABSTRACT TRUNCATED AT 250 WORDS)
在来自对照、乙醇和苯巴比妥（PB）处理大鼠的肝微粒体中，研究了甲苯在0.03 - 6.25 mM底物浓度下的体外代谢情况。通过高效液相色谱法测定了三种代谢物，即苯甲醇（BA）、邻甲酚和对甲酚。BA是甲苯的主要代谢物，而在对照大鼠的微粒体中，邻甲酚和对甲酚分别仅占总代谢物的1.1 - 1.5%和1.7 - 2.8%。乙醇处理对三种代谢物的百分比影响不大，但随着甲苯浓度的增加，PB将邻甲酚和对甲酚的百分比分别提高到了5.5%和8.0%。对照和乙醇处理大鼠的微粒体中，参与甲苯侧链羟基化的有两种不同的同工酶，其Km值不同。一种Km值较低（0.13 - 0.17 mM），乙醇处理可使其大幅诱导。另一种是高Km同工酶（0.60 - 0.87 mM）。PB诱导的同工酶与对照和乙醇处理大鼠微粒体中存在的高Km同工酶具有相似的Km值。对照大鼠微粒体中，两种同工酶参与了对甲酚的形成：低Km型与BA形成的低同工酶具有相似的值（0.15 mM），但高Km同工酶的值（2.04 mM）比对甲酚高同工酶的值大。在对照大鼠微粒体中仅检测到一种负责邻甲酚形成的酶，其Km（2.11 mM）与对甲酚高Km同工酶的Km相似。（摘要截取自250字）
