Metabolic studies in experimental liver disease resulting from D(+)-galactosamine administration.
1. In confirmation of previous work, administration of d(+)-galactosamine (0.5-0.75g/kg body wt.) to rats caused a hepatitis with histological evidence of liver damage and a 9-fold rise in aspartate aminotransferase activity in serum. 2. There was a significant elevation of blood lactate and pyruvate concentrations in 24h-starved rats treated with galactosamine but no change in the [lactate]/[pyruvate] ratio. 3-Hydroxybutyrate and acetoacetate concentrations in blood were decreased. 3. The changes in the concentrations of lactate, pyruvate and ketone bodies in the freeze-clamped liver were parallel to those observed in the blood. 4. In the livers of 24h-starved galactosamine-treated rats there were large increases in the concentrations of alanine (3-fold), citrate (5-fold), 2-oxoglutarate (4-fold), with smaller increases in malate, glutamate and aspartate. There was a 4-fold rise in the value of the mass-action ratio of the alanine aminotransferase system in the livers of galactosamine-treated rats when compared to controls. 5. There was a significant decrease in the activities of aspartate and alanine aminotransferases in the cytoplasm and the soluble fraction of sonicated homogenates of the livers of rats treated with galactosamine. The activity of phosphoenolpyruvate carboxylase was decreased by 75% of the control value. 6. Glucose synthesis from lactate in perfused livers from galactosamine-treated rats was inhibited 39% when compared with controls. 7. The results indicate that the conversion of lactate into glucose is decreased in the livers of galactosamine-treated rats and that this decrease may be due to the loss of phosphoenolpyruvate carboxylase from damaged hepatocytes.
D000090:Acetoacetates / Q000097:blood; D000409:Alanine / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood* / Q000378:metabolism; D001224:Aspartic Acid / Q000378:metabolism; D002262:Carboxy-Lyases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism*; D005688:Galactosamine; D005947:Glucose / Q000096:biosynthesis; D005971:Glutamates / Q000378:metabolism; D006885:Hydroxybutyrates / Q000097:blood; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism; D007773:Lactates / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D011773:Pyruvates / Q000097:blood / Q000378:metabolism; D051381:Rats
D000090:Acetoacetates; D005971:Glutamates; D006885:Hydroxybutyrates; D007657:Ketone Bodies; D007773:Lactates; D011773:Pyruvates; D001224:Aspartic Acid; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002262:Carboxy-Lyases; D005947:Glucose; D000409:Alanine