INFLUENCE OF D-GALACTOSAMINE ON THE SYNTHESIS OF SUGAR NUCLEOTIDES AND GLYCOCONJUGATES IN RAT HEPATOCYTES

Rat hepatocytes were incubated in the presence of a high concentration of the hepatopathogenic agent D-galactosamine (GalN), and the effect on the cellular concentrations of pyrimidine nucleotides and nucleotid e sugars was determined, The UTP pool became depleted. The pools of UM P and CMP in RNA decreased to 72%, indicative for an inhibition of RNA synthesis. UDP-HexNAc (where HexNAc is GlcNAc + GalNAc) and UDP-HexN (where HexN is GlcN + GalN) levels increased, and those of UDP-hexose and UDP-GlcA (where GlcA is glucuronic acid) decreased. The cellular c oncentration of CTP did not change, whereas that of CMP-NeuAc (where N euAc is N-acetylneuraminic acid) showed a 2-fold increase. Labelling w ith [C-14]orotic acid and [H-3]cytidine showed that the metabolic flow via the de novo pathway was not changed. The depletion of the so-call ed overflow pool of UTP [Pels Rijcken et al., Biochem, J., 293, 207-21 3, 1993] caused a release of the feedback inhibition by UTP and thus a n increased flow through the salvage pathway. Finally, it appeared tha t GalN, when added to hepatocytes, gives rise to a pool of UDP-GlcNAc (where GlcNAc is N-acetylglucosamine) that is separate from the pool o f UDP-GlcNAc that is derived from GlcN.