The role of L-serine dehydratase in the metabolism of L-serine in the perfused rat liver

Abstract

1. 1. To determine the role of L-serine dehydratase ( L-serine hydrolyase, deaminating, EC 4.2.1.13) in L-serine metabolism in the rat liver, experiments involving in situ liver perfusion, metabolite measurement in freeze-clamped tissues and enzyme activity determinations were conducted. 2. 2. Results from liver perfusion experiments showed that the maximal rate of gluconeogenesis from 10 mM L-serine was identical to that from equimolar quantity of L-lactate or pyruvate in starved animals. Combining L-serine and L-lactate in the perfusion medium did not produce glucose at a faster rate than with either L-lactate or L-serine alone. Glucose formation from L-serine or L-lactate was inhibited by 4.8 mM quinolinate which was reversible by 4.8 mM MnCl 2. 3. 3. Metabolite measurements revealed that perfusion with L-serine increased liver concentrations of pyruvate, lactate, aspartate, malate, and glutamate. The presence of 4.8 mM quinolinate further elevated the levels of aspartate, malate and glutamate. These metabolite levels dropped after the reversal of quinolinate inhibition by MnCl 2. 4. 4. The increase in glucogenic rate from L-serine by starvation was paralleled by similar increase in serine dehydratase activity in the supernatant fraction of liver homogenate and L-serine disappearance from the perfusion medium. 5. 5. These results strongly suggest that a major portion of L-serine was metabolized by L-serine dehydratase in the perfused rat liver.