Correlation of CYP and accessory protein (P450 oxidoreductase, POR; cytochrome b5A, CYB5A) concentrations with marker enzyme activities measured in the same set of dog liver microsomes (N = 59)
Propofol hydroxylation and tramadol n-demethylation were used as markers of CYP2B11 activity; dextromethorphan O-demethylation and tramadol O-demethylation were used as markers of CYP2D15 activity; omeprazole sulfonation was used as a marker of CYP3A activity; whereas cytochrome c oxidation was used as a marker of POR activity. Activity data are presented as an average of multiple independent replicates (number of replicates for each assay described in Materials and Methods). The average variation between replicate activity assays was less than 20%. Shown are the Spearman correlation coefficients (Rs) and the associated P values for each correlation.
| Spearman Correlation Coefficient (P Value) | ||||||
|---|---|---|---|---|---|---|
| Propofol Hydroxylation | Tramadol N-Demethylation | Dextromethorphan O-Demethylation | Tramadol O-Demethylation | Omeprazole Sulfonation | Cytochrome c Oxidation | |
| CYP1A1 | −0.01 (0.9) | −0.14 (0.3) | −0.28 (0.03) | −0.19 (0.2) | 0.17 (0.2) | 0.28 (0.03) |
| CYP1A2 | 0.18 (0.2) | 0.05 (0.7) | −0.17 (0.2) | −0.16 (0.2) | 0.26 (0.05) | 0.38 (0.003) |
| CYP2A13 | 0.16 (0.2) | 0.16 (0.2) | 0.43 (0.0008) | 0.38 (0.003) | 0.15 (0.3) | −0.23 (0.09) |
| CYP2A25 | 0.09 (0.5) | −0.08 (0.5) | 0.15 (0.3) | 0.1 (0.5) | 0.17 (0.2) | 0.26 (0.05) |
| CYP2B11 | 0.64 (<0.0001) | 0.74 (<0.0001) | 0.22 (0.1) | 0.13 (0.3) | 0.43 (0.0009) | 0.07 (0.6) |
| CYP2C21 | 0.36 (0.005) | 0.18 (0.2) | 0.26 (0.05) | 0.31 (0.02) | 0.01 (0.9) | 0.43 (0.0008) |
| CYP2C41a | 0.36 (0.005) | 0.39 (0.003) | 0.24 (0.06) | 0.22 (0.1) | 0.08 (0.5) | −0.02 (0.9) |
| CYP2D15 | 0.32 (0.01) | 0.32 (0.01) | 0.72 (<0.0001) | 0.67 (<0.0001) | 0.23 (0.08) | −0.1 (0.4) |
| CYP2E1 | −0.06 (0.7) | −0.13 (0.3) | 0.15 (0.3) | 0.19 (0.2) | −0.13 (0.3) | 0.06 (0.6) |
| CYP3A12 | 0.49 (0.0002) | 0.42 (0.001) | 0.21 (0.1) | 0.07 (0.6) | 0.71 (<0.0001) | 0.19 (0.2) |
| CYP3A26 | 0.49 (0.0002) | 0.42 (0.0009) | 0.34 (0.009) | 0.24 (0.07) | 0.5 (<0.0001) | −0.07 (0.6) |
| POR | 0.4 (0.002) | 0.2 (0.1) | 0.01 (0.9) | 0.05 (0.7) | 0.47 (0.0002) | 0.58 (<0.0001) |
| CYB5A | 0.58 (<0.0001) | 0.39 (0.003) | 0.38 (0.003) | 0.29 (0.02) | 0.48 (0.0002) | 0.42 (0.001) |
↵a Note that the results given for CYP2C41 are for the 12 dogs that express at least one copy of the CYP2C41 gene (four males and eight females).