TABLE 2

Substrate concentrations, Vmax, and Km values determined for the marker reactions in MMHHs from two independent studies

Vmax units are picomoles per minute per million cells; Km units are micromolars.

P450Marker ReactionStudySubstrate ConcentrationsVmaxMean VmaxKmMean KmKinetics
µM
CYP1A2Phenacetin deethylationa10, 15.625, 31.25, 62.5, 125, 250, 500, 1000518011.411TS (atypical)
20, 7.81, 15.625, 31.25, 62.5, 125, 250, 50010910.7TS (atypical)
CYP2A6Coumarin hydroxylation10, 0.937, 1.875, 3.75, 7.5, 15, 30, 601121.5ND
20, 0.156, 0.312, 0.625,1.25, 2.5, 5,101121.5SI (atypical)
CYP2B6Bupropion hydroxylation10, 15.625, 31.25, 62.5, 125, 250, 500, 10001311366967MM (typical)
20, 15.625, 31.25, 62.5, 125, 250, 500, 100014066MM (typical)
CYP2C8Amodiaquine deethylation10, 0.937, 1.875, 3.75, 7.5, 15, 30, 607585171.41.4MM (typical)
20, 0.937, 1.875, 3.75, 7.5, 15, 30, 602771.4MM (typical)
CYP2C9Diclofenac hydroxylation10, 3.125, 6.25, 12.5, 25, 50, 100, 20032732.4ND
20, 0.781, 1.562, 3.125, 6.25, 12.5, 25, 5032732.4MM (typical)
CYP2C19Mephenytoin hydroxylation10, 14.06, 28.12, 56.25, 112.5, 225, 450, 90049505545MM (typical)
20, 14.06, 28.12, 56.25, 112.5, 225, 450, 9005235MM (typical)
CYP2D6Dextromethorphan O-demethylationa10, 3.125, 6.25, 12.5, 25, 50, 100, 20028372.62.0TS (atypical)
20,0.47, 0.937, 1.875, 3.75, 7.5, 15, 30471.5TS (atypical)
CYP2E1Chlorzoxazone hydroxylation10, 31.25, 62.5, 125, 250, 500, 1000, 2000693462469465MM (typical)
20, 15.62, 31.25, 62.5, 125, 250, 500, 1000231462MM (typical)
CYP3A4Midazolam hydroxylation10, 0.937, 1.875, 3.75, 7.5, 15, 30, 601872153.73.5SI (atypical)
20, 0.312, 0.625,1.25, 2.5, 5,10, 202433.3MM (typical)
CYP3A4Testosterone hydroxylation10, 15.62, 31.25, 62.5, 125, 250, 500, 100076559273b70HK (atypical)
20, 15.62, 31.25, 62.5, 125, 250, 500, 100041867bHK (atypical)
  • HK, Hill kinetics; MM, Michaelis-Menten; ND, not determined; SI, substrate inhibition; TS, two-site.

  • a Only high-affinity enzyme values were reported for pathways following two-site kinetics.

  • b Values are S50 values equivalent to Km; Hill equation_n1 = 1.432 and n2 = 1.778.