Effect of 24 cytochrome P450 2D6 variants found in the Chinese population on the N-demethylation of amitriptyline in vitro

Figures & data

Figure 1. Michaelis–Menten curves of the enzymatic activity of the recombinant wild-type CYP2D6 protein and 24 variants towards AT (each point represents the mean ± SD of three or four separate experiments). The variants have been manually arranged into six different groups (A–F) in the order of the designated allele names.

Table 1. Kinetic parameters for catalytic activities of recombinant wild-type and mutant CYP2D6 proteins against AT.

Variants	Km (μM)	Vmax (pmol/min/pmol)	Intrinsic clearance (Vmax/Km)	Relative clearance
CYP2D6*1	20.37 ± 2.19	2.54 ± 0.56	0.1249 ± 0.0253	100.00%
CYP2D6*V342M	29.93 ± 3.66^a	2.67 ± 0.07^a	0.0892 ± 0.0200^a	71.42%^a
CYP2D6*94	23.25 ± 4.20^a	1.71 ± 0.07^a	0.0737 ± 0.0155^a	59.01%^a
CYP2D6*89	23.81 ± 2.34^a	1.42 ± 0.03^a	0.0594 ± 0.0126^a	47.56%^a
CYP2D6*91	27.34 ± 1.98^a	1.49 ± 0.02^a	0.0544 ± 0.0119^a	43.55%^a
CYP2D6*90	39.92 ± 3.31^a	2.15 ± 0.04^a	0.0539 ± 0.0130^a	43.15%^a
CYP2D6*98	32.22 ± 3.39^a	1.70 ± 0.04^a	0.0528 ± 0.0121^a	42.27%^a
CYP2D6*R344Q	33.85 ± 4.39^a	1.64 ± 0.05^a	0.0484 ± 0.0112^a	38.75%^a
CYP2D6*97	44.86 ± 5.29^a	1.87 ± 0.05^a	0.0416 ± 0.0103^a	33.31%^a
CYP2D6*F164L	55.15 ± 4.57^a	2.16 ± 0.05^a	0.0392 ± 0.0101^a	31.39%^a
CYP2D6*R497C	52.66 ± 2.58^a	2.04 ± 0.03^a	0.0388 ± 0.0099^a	31.06%^a
CYP2D6*V327M	48.63 ± 3.37^a	1.82 ± 0.03^a	0.0374 ± 0.0094^a	29.94%^a
CYP2D6*D336N	94.66 ± 11.91^a	3.23 ± 0.12^a	0.0341±±0.0099^a	27.30%^a
CYP2D6*F219S,	53.54 ± 4.81^a	1.78 ± 0.04^a	0.0333 ± 0.0085^a	26.66%^a
CYP2D6*88	49.19 ± 5.15^a	1.56 ± 0.01^a	0.0318 ± 0.0080^a	25.46%^a
CYP2D6*95	42.98 ± 4.03^a	1.35 ± 0.03^a	0.0313 ± 0.0077^a	25.06%^a
CYP2D6*R25Q	50.96 ± 6.00^a	1.46 ± 0.04^a	0.0286 ± 0.0073^a	22.90%^a
CYP2D6*2	128.23 ± 9.56^a	3.25 ± 0.08^a	0.0254 ± 0.0079^a	20.34%^a
CYP2D6*R440C	42.64 ± 6.35^a	0.99 ± 0.04^a	0.0233 ± 0.0057^a	18.65%^a
CYP2D6*E215K	128.31 ± 15.51^a	2.79 ± 0.11	0.0218 ± 0.0068^a	17.45%^a
CYP2D6*87	203.69 ± 33.32^a	2.43 ± 0.01	0.0119 ± 0.0042^a	9.53%^a
CYP2D6*10	229.14 ± 31.76^a	1.21 ± 0.06^a	0.0053 ± 0.0019^a	4.24%^a
CYP2D6*93	120.10 ± 12.32^a	0.55 ± 0.02^a	0.0046 ± 0.0014^a	3.68%^a
CYP2D6*92	ND	ND	ND	ND
CYP2D6*96	ND	ND	ND	ND

Note: Data are presented as the mean ± SD of three different expression experiments.

a p < 0.05 versus wild-type.