Summary of Work: Significant variations in the metabolism of various drugs and environmental chemicals which are metabolized via cytochrome P450 (CYP) enzymes exist between humans. Many of these interindividual variations are attributed to polymorphisms in the CYP2C subfamily of enzymes. Most recent studies identified new defective alleles of CYP2C19. Two allelic variants of CYP2C19 enzyme which contribute to the poor metabolizer phenotype in Caucasians were isolated and there metabolic activity was determined. CYP2C19*7 contained a single T?A nucleotide transversion in the invariant GT at the 5? donor site of intron 5. The second poor metabolizer allele, CYP2C19*8 consisted of a T358C nucleotide transition in exon 3 which resulted in Trp120Arg substitution. CYP2C19*8 was expressed in a bacterial expression system and microsomes were isolated. Reconstitution metabolism studies of recombinant proteins in vitro demonstrated that CYP2C19*8 protein exhibited approximately 90 and 70% reduction in the metabolism of S- mephenytoin and tolbutamide, respectively, when compared to the native CYP2C19*8 protein. . - Cytochrome P450 Human Recombinant enzymes HPLC Mephenytoin Omeprazole Tolbutamide Diclofenac