Table 1.

Models used to fit selective inhibition of the two reactions of P450 17A1 by S-orteronel

S, pregnenolone; P, 17α-OH pregnenolone; Q, DHEA; E, P450 17A1; E′, conformational variant of P450 17A1; I, S-orteronel. See Ref. 28 and Figs. S2 and S3 for input of many of the rate constants.

Basic model				Model with multiple conformations
Step	Reaction	k+	k−	Step	Reaction	k+	k−
		m−1 s−1	s−1			m−1 s−1	s−1
1	E + S ⇄ ES	0.62 × 106	0.29	1	E + S ⇄ ES	0.62 × 106	0.29
2	ES → EP	0.43a		2	ES → EP	0.43a
3	E + P ⇄ EP	0.79 × 106	0.41	3	E + P ⇄ EP	0.79 × 106	0.41
6	EP → EQ	0.077a		4	EP ⇄ E′P	1.0	1.0
8	E + Q ⇄ EQ	0.45 × 106	0.77	5	E′ + P ⇄ E′P	0.79	0.42
10	E + I⇄ EI	3.0 × 106	0.01	6	EP → EQ	0.077a
				7	E′P → E′Q	0.077a
				8	E + Q ⇄ EQ	0.45 × 106	0.77
				9	E′ + Q ⇄ E′Q	0.45 × 106	0.77
				10	E + I ⇄ EI	3.0 × 106	0.01
				11	E′ + I ⇄ E′I	3.0 × 106	0.001

^a First-order rate constant for irreversible reaction, in s⁻¹.