Saccharomyces cerevisiae: an alternative source for human microsomal liver enzymes and its use in drug interaction studies.
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.
Eugster
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Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach.
Sengstag
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D000927:Anticonvulsants / Q000494:pharmacology; D001571:Benzoflavones / Q000494:pharmacology; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D003001:Cloning, Molecular; D019388:Cytochrome P-450 CYP1A2; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D004347:Drug Interactions; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D014635:Valproic Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D000927:Anticonvulsants; D001571:Benzoflavones; D065607:Cytochrome P-450 Enzyme Inhibitors; D018076:DNA, Complementary; D002220:Carbamazepine; C011512:alpha-naphthoflavone; D014635:Valproic Acid; D003577:Cytochrome P-450 Enzyme System; D019388:Cytochrome P-450 CYP1A2; D010089:Oxidoreductases, N-Demethylating; D004851:Epoxide Hydrolases; C012227:carbamazepine epoxide; D007654:Ketoconazole; C004651:dipropylacetamide