TABLE 1

Kinetic parameters for dextromethorphan O-demethylation catalyzed by wild and mutant types of CYP2D6 expressed in E. coli membranes

Dextromethorphan (3.5-2000 μM) was incubated with membrane fractions prepared from genetically engineered E. coli. Kinetic parameters were calculated by nonlinear regression analysis. Each value represents the mean ± S.D. from three determinations.

CYP2D6 Allele	CYP2D6 Protein	Amino Acid Changes	O-Demethylation					7-Hydroxylation^a
CYP2D6 Allele	CYP2D6 Protein	Amino Acid Changes				K_m	V_max	V_max/K_m	K_m	V_max	V_max/K_m
			μM	nmol/min/nmol CYP2D6	ml/min/nmol CYP2D6	μM	nmol/min/nmol CYP2D6	ml/min/nmol CYP2D6
* 1	CYP2D6.1	None	10 ± 1	6.3 ± 0.9	0.63	N.D.	N.D.	N.D.
* 10	CYP2D6.10	P34S, S486T	63 ± 7	1.2 ± 0.2**	0.019	N.D.	N.D.	N.D.
* 49	CYP2D6.49	P34S, F120I, S486T	323 ± 44**^,^‡	0.9 ± 0.1**	0.003	391 ± 23	0.8 ± 0.2	0.002
* 72	CYP2D6.72	P34S, E383K, S486T	87 ± 21*	0.7 ± 0.3**^,^†	0.008	N.D.	N.D.	N.D.

N.D., product not detectable.
↵ a Hydroxylation velocity was determined as the peak area ratio of metabolite to dextrorphan standard.
↵* P < 0.05 and ** P < 0.01, significantly different from wild-type CYP2D6*1 by Dunnett's test.
↵† P < 0.05 and ^‡P < 0.01, significantly different from CYP2D6*10 by Dunnett's test.