Kinetics of hepatic alanine uptake and urea synthesis in pigs

The kinetics of hepatic alanine uptake and urea synthesis in relation to sinusoid alanine concentration was investigated in seven anesthetized pigs weighing 63 kg, using liver vein catheterizations. Each experiment consists of four steady-state periods of 40 min with alanine concentrations in the range of 0.4-27 mmol/l. The process rates were measured as the products of transhepatic concentration gradients and hepatic blood flow rate, determined by indocyanine green. The data suggest that both processes follow saturation kinetics, that there exists a sinusoidal concentration of alanine below which net removal is limited, and that urea synthesis consists of two components: one alanine independent and one depending on alanine concentration according to Michaelis-Menten kinetics. The kinetic parameters were estimated iteratively by the maximum likelihood method. The maximum rate of alanine uptake was 1.13 +/- 0.74 mmol.min-1.kg liver wt-1 (mean +/- SD), the alanine concentration resulting in half-maximum alanine uptake rate was 1.69 +/- 0.99 mmol/l, and the removal-limiting alanine concentration was 0.27 +/- 0.09 mmol/l. The maximum rate of urea-N synthesis was 1.49 +/- 0.87 mmol.min-1.kg liver wt-1, the alanine concentration resulting in half-maximum urea-N synthesis rate was 2.32 +/- 1.11 mmol/l, and the alanine concentration-independent urea-N synthesis rate was 0.13 +/- 0.10 mmol.min-1.kg liver wt-1.