TABLE 4

Derived kinetic constants for 1-NP glucuronidation by UGT1A3 and UGT1A4 chimeras and mutants Data shown as parameters ± S.E. of parameter fit.

Enzyme
Km a , b
Ksi a
Vmax c
CLintd
μM μM pmol/min/mg μl/min/mg
UGT1A3 2330 ± 24a 916 ± 13 300 ± 2 0.13
UGT1A3–4 314 ± 2b 351 ± 1 1.12
UGT1A3–4-3 342 ± 18a 2207 ± 125 127 ± 3 0.37
UGT1A3(I36T) 3399 ± 360a 437 ± 42 57 ± 3 0.01
UGT1A3(H40P) N.A. N.A. N.A. N.A.
UGT1A4 N.A. N.A. N.A. N.A.
UGT1A4–3 N.A. N.A. N.A. N.A.
UGT1A4–3-4 N.A. N.A. N.A. N.A.
UGT1A4(T36I) 137 ± 2b - 116 ± 1 0.84
UGT1A4(P40H)
N.A.
N.A.
N.A.
N.A.

  • N.A., no activity

  • ↵ a From fitting to the substrate inhibition equation

  • ↵ b From fitting to the Michaelis Menten equation

  • ↵ c Normalized for expression relative to UGT1A3

  • ↵ d Calculated as Vmax/Km