PubMed Health⌕ Search

Biomedical subjects

G Grimber

Publications and source records attributed to G Grimber.

44 records · Page 3Linked to original sources
PubMed1983

Action of the antiepileptic drug, valproic acid, on fatty acid oxidation in isolated rat hepatocytes.

Valproate at 0.1 to 5 mM strongly inhibited oxidation of 1-(14C)-palmitate in isolated rat hepatocytes. Valproate at the same concentrations markedly decreased ketogenesis from 1 mM oleate. Valproate in a dose up to 5 mM did not significantly affect cellular concentration of ATP but lowered beta-hydroxybutyrate/acetoacetate and lactate/pyruvate ratios which paralleled its effect on ketogenesis. Moreover concomitant acetyl-CoA levels were drastically decreased by valproate. From this it may be concluded that inhibition of fatty acid oxidation by valproate results in reduced production of two carbons units and a drop of NADH/NAD+ ratio in rat hepatocyte. This suggests that valproate seriously interferes with beta-oxidation of physiological long-chain fatty acids.

Animals↗
PubMed1983

Characterization of enzymatic deficiencies of branched chain amino-acid catabolism in human fibroblasts by genetic complementation.

Leucine and Isoleucine metabolism in cultured skin fibroblasts from patients with leucinosis, beta-Ketothiolase deficiency, propionic, methylmalonic and isovaleric acidemia, was compared with that in normal fibroblasts. A simple assay was developed using (U14C) Isoleucine and (U14C) Leucine as substrates. Radioactive incorporation into protein aminoacids were measured. The (U14C) branched chain aminoacid incorporation into proteins provides an estimation of the protein synthesis and the incorporation ratio (14C) Aspartate + (14C) Glutamate/(14C) branched chain aminoacid, measures the integrity of the metabolic pathway. Complementation tests permits to characterize the genetic defect. The incorporation ratio was significantly decreased in blocked pathways, namely in leucinosis and isovaleric acidemia in the presence of (U14C) Leucine and in Leucinosis, beta-Ketothiolase deficiency, propionic and methylmalonic acidemia in the presence of (U14C) Isoleucine. There was a significant restoration of activity in mutant strains with distinct genetic defects after polyethylene-glycol fusion. This assay provides a valuable tool to screen for enzymatic deficiencies of branched chain aminoacid catabolism.

Acetyl-CoA C-Acyltransferase↗
PubMed1983

Developmental changes of citrullinogenesis, mitochondrial N-acetylglutamate content and N-acetylglutamate synthetase in fetal and neonatal rats.

A low citrullinogenesis (less than 60 per cent of the adult value) was observed throughout the suckling period when mitochondria isolated from newborn rat liver were incubated in vitro with L-glutamate or succinate as oxidizable substrates. The adult value was reached after weaning. From birth to weaning, intact mitochondria synthesized more citrulline when supplemented with L-glutamate than with succinate. The low citrullinogenesis could not be explained by low carbamoylphosphate synthetase-I and ornithine transcarbamoylase activities that reached adult values at birth. The decreased citrullinogenesis seen for the first three days of life seemed to be related to the low intramitochondrial concentration of N-acetylglutamate, an activator of the carbamoylphosphate synthetase-I. The concentration of this activator did not differ from that reported for adult rat liver mitochondria after the fourth day of life. The discrepancy between the normal value of N-acetylglutamate concentration and the low activity of the N-acetylglutamate synthetase (15 to 30 per cent of the adult activity) is discussed on the basis of acetyl-CoA or L-glutamate availability in mitochondria isolated from newborn or young rats.

Acetyltransferases↗
PubMed1981

[Lysinuric protein intolerance: a severe hyperammonemia secondary to l-arginine deficiency (author's transl)]].

Lysinuric protein intolerance is an autosomal recessive disease, due to a defect in intestinal, renal and hepatic dibasic amino acid transport. Two new cases in the same family are reported. The disease appears progressively during the first months of life with failure to thrive, anorexia, vomiting, diarrhea, hepatosplenomegaly, muscular weakness, osteoporosis, anemia, leukothrombocytopenia, hyperammonemia and orotic aciduria after a high-protein intake. Hyperdibasicamino-aciduria was associated with subnormal plasma concentrations of the same aminoacids. Oral l-arginine, l-ornithine, l-lysine, and lysyl-glycine loads confirmed the diagnosis. The supplementation of the diet with l-citrulline resulted in normal levels of blood ammonia. However, hepatosplenomegaly, muscular weakness, osteoporosis remained unchanged and growth was not improved. These may be due to lysine deficiency.

Amino Acid Metabolism, Inborn Errors↗