Enzyme Source | IFA | IFA metabolism | Activity Ratios | ||||
---|---|---|---|---|---|---|---|
4-OH-IFA3-a | Total DCl-IFA3-a | Sum (4-OH + DCl)3-a | S/R DCl | 4OH/DCl | % DCl3-b | ||
2B6 | R | ≤0.4 | 9.77 | ∼9.77 | ≤0.04 | ≥96 | |
S | 2.08 | 11.47 | 13.55 | 1.17 | 0.18 | 85 | |
3A4 | R | 19.23 | 9.12 | 28.35 | 2.11 | 32 | |
S | 6.70 | 34.51 | 41.21 | 3.78 | 0.19 | 84 | |
3A5 | R | 2.32 | 0.50 | 2.82 | 4.64 | 17 | |
S | 0.29 | 3.38 | 3.67 | 6.76 | 0.09 | 92 | |
HLS2 | R | 0.34 ± 0.00 | 0.38 ± 0.08 | 0.72 | 0.90 | 53 | |
S | 0.32 ± 0.02 | 1.20 ± 0.14 | 1.52 | 3.16 | 0.27 | 79 | |
HLS9 | R | 0.71 ± 0.06 | 0.51 ± 0.05 | 1.22 | 1.39 | 42 | |
S | 0.53 ± 0.03 | 1.36 ± 0.04 | 1.88 | 2.67 | 0.39 | 72 | |
HLS18A | R | 0.24 ± 0.01 | 0.13 ± 0.00 | 0.37 | 1.85 | 35 | |
S | 0.18 ± 0.02 | 0.46 ± 0.05 | 0.64 | 3.54 | 0.39 | 72 | |
HLS25 | R | 0.35 ± 0.02 | 0.07 ± 0.01 | 0.42 | 5.00 | 17 | |
S | 0.23 ± 0.01 | 0.17 ± 0.03 | 0.40 | 2.43 | 1.35 | 43 | |
HLS27 | R | 0.39 ± 0.05 | 0.09 ± 0.01 | 0.48 | 4.33 | 19 | |
S | 0.27 ± 0.01 | 0.24 ± 0.00 | 0.51 | 2.67 | 1.13 | 47 | |
HLS28 | R | 0.41 ± 0.02 | 0.12 ± 0.01 | 0.53 | 3.42 | 23 | |
S | 0.33 ± 0.04 | 0.66 ± 0.01 | 0.99 | 5.50 | 0.50 | 67 | |
HLS35 | R | 0.42 ± 0.02 | 0.15 ± 0.03 | 0.57 | 2.80 | 26 | |
S | 0.38 ± 0.01 | 0.22 ± 0.05 | 0.60 | 1.47 | 1.73 | 37 | |
HLS36 | R | 0.45 ± 0.05 | 0.29 ± 0.01 | 0.74 | 1.55 | 39 | |
S | 0.28 ± 0.01 | 0.96 ± 0.01 | 1.24 | 3.31 | 0.29 | 77 |
↵3-a Activities for CYPs 2B6, 3A4 and 3A5 are expressed in units of nmol metabolite/min/nmol P450. Liver microsomal activities are in units of nmol metabolite/min/mg protein. Data are based on mean ± one-half range of duplicate determinations. TotalN-dechloroethylation is equal to the sum of the activities measured for the formation of two isomeric DCl metabolites.
↵3-b Percentage N-dechloroethylation calculated as [total DCl-IFA × 100]/(Total DCl-IFA + 4-OH-IFA), i.e., the contribution of N-dechloroethylation to total IFA metabolism (4-OH + N-DCl).