TABLE 1

Degradation rates (kdeg) and half-lives (t1/2) determined using HepatoPac-SILAC for CYP3A4

Data were calculated from four donors and are reported as mean and S.D. The average kdeg and t1/2 values determined for the three nonarginine-containing CYP3A4 peptides were 0.023 ± 0.002 h−1 and 29.7 ± 2.3 hours, respectively. The kdeg and t1/2 values for the arginine-containing peptide (EVTNFLR) were 0.033 ± 0.005 h−1 and 21.0 ± 2.6 hours, respectively. Recent kdeg and t1/2 value determinations for CYP3A4 using HepatoPac by mRNA following siRNA or interleukin 6 inhibition were 0.0240 h−1 and 28.9 hours, respectively (Ramsden et al., 2015); and by mRNA following induction they were 0.0261 h−1 and 26 hours, and 49 hours by activity following rifampicin induction (Dixit et al., 2016).

P450Peptideakdegt1/2
h−1h
CYP3A4SLLSPTFTSGK0.023 ± 0.00229.6 ± 1.9
CYP3A4DVEINGMFIPK0.023 ± 0.00129.6 ± 1.0
CYP3A4YWTEPEK0.023 ± 0.00129.8 ± 0.8
  • a The SRM parameters of the specific peptides used for LC-MS/MS protein measurements are provided in Supplemental Table 2.