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Biomedical subjects

P Parvy

Publications and source records attributed to P Parvy.

At least 55 records · Page 3Linked to original sources
PubMed1989

Clinical approach to inherited metabolic diseases in the neonatal period: a 20-year survey.

Every newborn with unexplained neurological deterioration, ketosis, metabolic acidosis or hypoglycaemia should be suspected of having an inherited error of intermediary metabolism. Many of these conditions can be diagnosed clinically with the aid of simple laboratory investigations. Since a substantial number of these diseases respond well to treatment but may otherwise be fatal, and in order to assure adequate prenatal diagnosis in subsequent pregnancies, a high index of suspicion and rapid diagnosis are necessary in the face of the clinical presentations described. According to three major clinical presentations observed in 218 neonates with inborn errors of intermediary metabolism (neurological distress 'intoxication' type, neurological distress 'energy-deficiency' type and hypoglycaemia with liver dysfunction) and according to the proper use of few laboratory investigations, we propose a method of diagnosis which groups these children into five categories. Initial therapy, and sophisticated investigations can be planned on the basis of this grouping.

Energy Metabolism↗
PubMed1984

Potentiation by ammonia of the metabolic effects of pent-4-enoate in isolated rat hepatocytes.

The metabolic effects of pent-4-enoate were studied in isolated rat hepatocytes; 1 mM-pent-4-enoate did not significantly inhibit gluconeogenesis from lactate, alanine and glycerol, but significantly decreased glucose synthesis from pyruvate. The addition of 1 mM-NH4Cl led to a drastic inhibition of glucose synthesis from all these substrates. In hepatocytes incubated with 10 mM-alanine and 1 mM-oleate, pent-4-enoate at 0.05-1 mM slightly inhibited glucose synthesis and ketogenesis. The addition of ammonia resulted in a dramatic potentiation of the metabolic effects of pent-4-enoate. Half-maximum effect of ammonia was observed at 0.2 mM concentration. Concomitant cellular concentrations of ATP and acetyl-CoA were also decreased by the addition of ammonia, as were lactate/pyruvate ratio and beta-hydroxybutyrate/acetoacetate ratio. These data suggest that ammonia seriously interferes with the cellular metabolism of pent-4-enoate and leads to a dramatic potentiation of its effects.

Acetyl Coenzyme A↗
PubMed1983

Role of N-acetylglutamate and acetyl-CoA in the inhibition of ureagenesis by isovaleric acid in isolated rat hepatocytes.

1 and 10 mmol/l isovalerate strongly inhibited urea synthesis in isolated rat hepatocytes incubated with 10 mmol/l alanine and 3 mmol/l ornithine. Isovalerate also markedly decreased N-acetylglutamate levels, and the decrease correlated with the inhibition of urea synthesis by isovalerate. This compound also lowered cellular levels of acetyl-CoA, a substrate of N-acetylglutamate synthase (EC 2.3.1.1). Isovalerate did not significantly affect the cellular levels of ATP and had no direct effect on N-acetylglutamate synthase activity. These results suggest that the inhibition of urea synthesis by isovalerate is due to decrease in N-acetylglutamate levels.

Acetyl Coenzyme A↗
PubMed1983

Inhibition of ureagenesis by valproate in rat hepatocytes. Role of N-acetylglutamate and acetyl-CoA.

Valproate (0.5-5 mM) strongly inhibited urea synthesis in isolated rat hepatocytes incubated with 10 mM-alanine and 3 mM-ornithine. Valproate at the same concentrations markedly decreased concentrations of N-acetylglutamate, an essential activator of carbamoyl-phosphate synthetase I (EC 6.3.4.16), in parallel with the inhibition of urea synthesis by valproate. This compound also lowered the cellular concentration of acetyl-CoA, a substrate of N-acetylglutamate synthase (EC 2.3.1.1); glutamate, aspartate and citrulline were similarly decreased. Valproate in a dose up to 2 mM did not significantly affect the cellular concentration of ATP and had no direct effect on N-acetylglutamate synthesis, carbamoyl-phosphate synthetase I and ornithine transcarbamoylase (EC 2.1.3.3) activities.

Acetyl Coenzyme A↗
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↗
PubMed1982

Acute effects of glucagon on citrulline biosynthesis.

Mitochondria isolated from livers of rats fed on different diets showed altered capacity to synthesize citrulline. Glucagon, 15 min after injection, increases citrulline biosynthesis, except after the high-protein diet. A significant correlation between citrulline biosynthesis and N-acetylglutamate content with and without glucagon treatment was shown when rats were fed on a standard or a carbohydrate diet. Different diets modified carbamoyl phosphate synthetase I (EC 6.3.4.16) and N-acetylglutamate synthase (acetyl-CoA:L-glutamate N-acetyltransferase, EC 2.3.1.1) activities. Glucagon did not modify these activities.

Animals↗
PubMed1982

Blood and urinary amino acids in children receiving total parenteral nutrition.

Plasma concentrations and urinary outputs of amino acids were estimated in nineteen patients receiving intravenous hyperalimentation to evaluate the adequacy of dosage and composition of the infusates for the maintenance of normal blood concentrations of essential amino acids. The use of high concentrations of branched chain amino acids seems to be appropriate for valine and isoleucine but not for leucine. The high concentration of cysteine in the infusates used induces a very high urinary excretion of cysteine and cystine and are ineffective to bring the decreased plasma cystine levels back to normal.

Journal Article↗