Table 2.
steady-state kinetic constants for individual metabolitesc | |||||
---|---|---|---|---|---|
pathway | step | substrate | Vmax b | Km (μM) | V/K |
pathway 1 | 1.1 | terbinafine | N-methyl-1-naphthyl-methylamine | ||
1000 ± 65 | 150 ± 25 | 6.7 | |||
1.2 | N-methyl-1-naphthyl methylamine | 1-napthaldehyde | |||
390 ± 28 | 110 ± 22 | 3.5 | |||
pathway 2 | 2.1 | terbinafine | desmethyl-terbinafine | ||
1300 ± 63 | 86 ± 13 | 15 | |||
2.2a | desmethyl-terbinafine | 1-naphthyl-methylamine | |||
570 ± 44 | 410 ± 54 | 1.4 | |||
2.2b | desmethyl-terbinafine | 1-naphthaldehyde | |||
5900 ± 430 | 520 ± 63 | 11 | |||
pathway 3d,e | 3.1 | terbinafine | 1-naphthaldehyde | ||
5700 ± 190 | 110 ± 11 | 52 |
Data fit best to the Michaelis–Menten equation over the Hill equation (P < 0.05) shown in Figures 3, 4, and 5. Values shown with standard deviations.
Units are pmol/min/nmol of protein.
Quantitation of TBF-A catalytic efficiency was not possible due to variable Vmax values, while the Km values were consistent.
Pathway Step 3.2 was not studied due to the absence of authentic standards and low efficiency of the previous step in a human liver microsomal enzymatic system that obviates the significance of this pathway for TBF-A.
Limit of quantitation was calculated as the standard deviation of response divided by the slope of the standard curve.