The hepatocellular influx of leucine was investigated in the perfused
rat liver using the multiple indicator-dilution technique. The cellula
r influx of leucine was saturable and the K-m and V-max values were 5.
3 +/- 1.8 mM and 194 +/- 25 nmol/s/g of liver, respectively. These wer
e similar to those reported in cell membrane preparations. Previous st
udies have indicated that oxidative injury impairs the activity of mem
brane transporters. Perfusion with 10 mM hydrogen peroxide for 3 min c
aused a significant reduction in leucine influx from 7.4 +/- 1.4 nmol/
s/g of liver to 4.6 +/- 1.0 nmol/s/g of liver (P = 0.007) with a perfu
sate leucine concentration of 0.13 mu M. This was not associated with
any significant change in the extracellular volume (0.31 +/- 0.08 ml/g
of liver vs. 0.32 +/- 0.01 ml/g of liver). This confirms that oxidati
ve injury in the liver is associated with impairment of membrane trans
port and extends the observation to the transport of leucine.