TABLE 1

Metabolism of nicotine by P450 2A13, P450 2A3, and P450 2A5: formation of the Δ^5′(1′)iminium ion versus cotinine P450 2A enzymes were incubated with [5-³H]nicotine (specific activity 1–200 μM) at 37°C for 30 min in the presence of human liver cytosol as described under Materials and Methods. The formation of product was measured using HPLC with radioflow detection.

	Product Formation
Nicotine	P450 2A13					P450 2A3				P450 2A5
	Δ^5′(1′)-Iminium Ion	Cotinine	Total^a	Δ^5′(1′)-Iminium Ion	Cotinine	Total	Δ^5′(1′)-Iminium ion	Cotinine	Total
pmol
1.0	0	24	24	2.6	19	21.6	3.4	35	38
2.5	3.0	59	62	5.5	39	45	6.5	69	76
5	8.1	113	121	8.2	58	66	14	109	123
10	36	189	225	12.1	88	100	24	180	204
25	210	315	525	21.1	122	143	36	223	259
50	476	304	780	23.2	144	167	52	262	314
100	909	272	1180	30.2	139	169	60	252	312
200	1180	316	1490	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.

N.D., not determined.
↵ a The sum of the nicotine Δ^5′(1′)iminium ion and cotinine