Tylenol is cleared from the body in the form of a glucuronide, whose carbon skeleton originates from the hexose moiety of hepatic UDP-glucose, providing a means of measuring tracer incorporation into the hepatic gluconeogenic hexose pool.
Phenylacetic acid is cleared by forming a conjugate with hepatic glutamine.
Since the glutamine carbon skeleton is derived from a -ketoglutarate, this metabolite provides information on tracer incorporation into the hepatic citric acid cycle. Our preliminary studies with normal, fasted subjects indicate that glucose and glucuronide isotopomer distributions are identical to each other, and they both report high anaplerotic and pyruvate recycling fluxes. Net gluconeogenic efflux was about 2.4 times the flux through citrate synthase. However, the phenylacetylglutamine isotopomer distribution was significantly different from that of the hexoses, resulting in significantly higher estimate of pyruvate recycling and lower estimate of gluconeogenic efflux. These differences between hepatic hexose and glutamine isotopomer distributions may reflect metabolic heterogeneity within the liver.