Eugster H P, Sengstag C
Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach.
Toxicology. 1993 Oct 5;82(1-3):61-73. doi: 10.1016/0300-483x(93)90060-6.
Heterologous expression of human cDNAs in the yeast Saccharomyces cerevisiae represents an attractive alternative source of human enzymes and allows metabolic studies to be performed without the need of human tissue. Here we report on the functional expression of human microsomal epoxide hydrolase (hmEH) and cytochrome P450 1A1 and 1A2 in yeast. Microsomal fractions of corresponding yeast strains exhibited enzyme specific activities which allowed the characterization of the heterologous enzymes. The use of these microsomes enabled us to study drug interactions on the respective enzymes with pharmacologically relevant drugs such as carbamazepine epoxide, valpromide and ketoconazole.
在酿酒酵母中对人类cDNA进行异源表达,是获取人类酶的一种有吸引力的替代来源,并且无需使用人体组织就能开展代谢研究。在此,我们报告人类微粒体环氧化物水解酶(hmEH)以及细胞色素P450 1A1和1A2在酵母中的功能表达。相应酵母菌株的微粒体组分表现出酶的比活性,这使得我们能够对异源酶进行特性描述。使用这些微粒体使我们能够研究卡马西平环氧化物、丙戊酰胺和酮康唑等具有药理学相关性的药物与相应酶之间的药物相互作用。