PubMed Health⌕ Search

Biomedical subjects

J M Trijbels

Publications and source records attributed to J M Trijbels.

At least 19 recordsLinked to original sources
PubMed1992

Persistent hypermethioninaemia with dominant inheritance.

A clinically benign form of persistent hypermethioninaemia with probable dominant inheritance was demonstrated in three generations of one family. Plasma methionine concentrations were between 87 and 475 mumol/L (normal mean 26 mumol/L; range 10-40 mumol/L); urinary methionine and homocystine concentrations were normal. Plasma homocystine, cystathionine, cystine and tyrosine were virtually normal. The concentrations in serum and urine of metabolites formed by the methionine transamination pathway were normal or moderately elevated. Methionine loading of two affected family members revealed a diminished ability to catabolize methionine, but the activities of methionine adenosyltransferase and cystathionine beta-synthase were not decreased in fibroblasts from four affected family members. Fibroblast methylenetetrahydrofolate reductase activity and its inhibition by S-adenosylmethionine were also normal, indicating normal regulation of N5-methyltetrahydrofolate-dependent homocysteine remethylation. Serum folate concentrations were not increased. The findings in this family differ from those previously described for known defects of methionine degradation. Since the hepatic and fibroblast isoenzymes of methionine adenosyltransferase differ in their genetic control, this family's biochemical findings appear consistent with a mutation in the structural gene for the hepatic methionine adenosyltransferase isoenzyme.

Amino Acid Metabolism, Inborn Errors↗
PubMed1992

Prenatal diagnosis of systemic disorders of the respiratory chain in cultured amniocytes and chorionic villus fibroblasts by studying the formation of lactate and pyruvate from glucose.

Formation of lactate and pyruvate from glucose was studied in cultured amniocytes and chorionic villus fibroblasts from controls, either untreated or treated with azide, an inhibitor of cytochrome c oxidase, or other inhibitors of the mitochondrial respiratory chain. Amniocytes with an established cytochrome c oxidase deficiency were also investigated. Control amniocytes treated with azide as well as cytochrome c oxidase deficient amniocytes displayed strongly increased lactate-to-pyruvate ratios after incubation with glucose, compared to control cells. Elevated lactate-to-pyruvate ratios were also found in chorionic villus fibroblasts in which complexes I, III or IV were inhibited by rotenone, antimycin or azide, respectively. We conclude that measurement of lactate and pyruvate production from glucose in cultured amniocytes and/or chorionic villus fibroblasts allows adequate prenatal diagnosis of systemic cytochrome c oxidase deficiency and presumably of other systemic deficiencies of mitochondrial respiratory chain enzymes.

Amnion↗
PubMed1992

Combined deficiencies of the pyruvate dehydrogenase complex and enzymes of the respiratory chain in mitochondrial myopathies.

In six patients with mitochondrial (encephalo-) myopathy investigations of skeletal muscle revealed a defect of pyruvate dehydrogenase complex (PDHC) in combination with one or more respiratory chain complex deficiencies. A combination of defects of this kind has not been reported previously. Five of the six patients presented within the 1st year of life and had a severe clinical course. Intrafamilial variability of the clinical course in dizygotic twins both suffering from a cytochrome c oxidase deficiency and one of them also from a PDHC deficiency suggests an additional effect of PDHC deficiency on the clinical symptoms. Immunoblot studies of PDHC in five of the patients revealed no abnormalities in their subunit pattern, rendering a defect of mitochondrial protein import or assembly unlikely. The finding of a combined PDHC and respiratory chain deficiency has implications for the diagnostic approach, for therapy and genetic counselling. The exact pathogenetic mechanism of this combination of defects remains to be elucidated.

Female↗
PubMed1992

Myopathology and a mitochondrial DNA deletion in the Pearson marrow and pancreas syndrome.

A patient with the Pearson marrow and pancreas syndrome is presented. She showed an anaemia with neutropenia and thrombopenia, failure to thrive, diarrhoea, disturbed glucose homeostasis and lactic acidosis. An exocrine pancreatic insufficiency was lacking. The disease followed a fatal course. Biochemical investigations of skeletal muscle revealed a disturbed mitochondrial energy metabolism, while many ultrastructural abnormal features were observed in the muscle tissue. Molecular genetic studies showed a de novo deletion in the mitochondrial DNA (mtDNA), different in size from the already published deletions and flanked by two 4 bp direct repeats, interspaced by 4-5 non-repeated nucleotides. mtDNA from 12 other tissues showed the same deletion in different percentages. No obvious relation between these percentages and tissue dysfunction was found. In spite of an open reading frame of 74 codons, only little transcription product of the genomic region resulting from the deletion was found.

B-Lymphocytes↗
PubMed1992

Postnatal development of pyruvate oxidation in quadriceps muscle of the rat.

In order to evaluate the age dependency of enzymes involved in the energy-generating system, skeletal muscle specimens from rats of different ages were investigated for several mitochondrial enzymes. [1-14C]pyruvate (+/- ADP) oxidation rates and pyruvate dehydrogenase complex (PDHC) activity increased significantly from low early values during the neonatal period to nearly adult values at the end of the suckling period. Other enzymes of the pyruvate oxidation route such as citrate synthase and cytochrome c oxidase showed similar patterns of development. Immunoblot studies of PDHC detected a clear increase in the intensity of the bands of the alpha subunits of E1 (pyruvate dehydrogenase) and E2 (dihydrolipoyl transacetylase) within the first 3 weeks of life. The ratio between the individual PDHC proteins indicated that E1 alpha, the regulatory subunit of the multienzyme complex, is the most rapidly increasing protein with age.

Acetyltransferases↗
PubMed1992

Enzyme activities of the mitochondrial energy generating system in skeletal muscle tissue of preterm and fullterm neonates.

Quadriceps muscle specimens from autopsy of 28 neonates (gestational age 25-42 weeks) were investigated to determine pyruvate and malate oxidation rates and several enzymes of the mitochondrial oxidative process. In general, the levels of all mitochondrial parameters measured, including carnitine levels, were lower in the neonates who died within the first week of life than those in the control group (age > 5 years). Pyruvate and malate oxidation rates (P < 0.05), activities of pyruvate dehydrogenase complex (P < 0.10) and succinate: cytochrome c oxidoreductase (P < 0.05) increased significantly with gestational age. Pyruvate oxidation rates (P < 0.05) as well as activities of citrate synthase (P < 0.05) and NADH:Q1 oxidoreductase (P < 0.05) were significantly lower in the group of very preterm infants at an age of 1-7 days compared with very preterm infants at an age between 3-8 weeks. We conclude from our study that special reference values are necessary for a correct biochemical diagnosis of mitochondrial encephalomyopathies in the neonatal period. Differences between preterm and fullterm children of the same age (1 week) indicate a maturational process in human muscle tissue during gestation. Comparison of two different age groups within the very preterm neonates point to a postnatal maturation of the mitochondrial energy metabolism, at least in preterm neonates.

Carnitine↗
PubMed1991

Immunochemical and biochemical studies of fatty acid oxidation in fibroblasts of Zellweger and X-linked adrenoleukodystrophy patients.

Immunoblot analyses of peroxisomal beta-oxidation enzymes showed that subunit A of acyl-CoA oxidase gave a stronger immunoreaction in fibroblasts of Zellweger and X-linked adrenoleukodystrophy patients than in those of controls. Subunits B and C and 3-ketoacyl-CoA thiolase were detected in fibroblasts of controls and X-linked adrenoleukodystrophy patients, but not of Zellweger patients. Total oxidation of palmitic and lignoceric acid was normal in homogenates of fibroblasts from Zellweger and X-linked adrenoleukodystrophy patients. The peroxisomal oxidation of both acids was only deficient in Zellweger patients. These data may not reflect the situation in vivo, as is evident from the accumulation of very-long-chain fatty acids in Zellweger and X-linked adrenoleukodystrophy patients.

Acetyl-CoA C-Acyltransferase↗
PubMed1991

Peroxisomal oxidases and catalase in liver and kidney homogenates of normal and di(ethylhexyl)phthalate-fed rats.

1. Activities of peroxisomal oxidases and catalase were assayed at neutral and alkaline pH in liver and kidney homogenates from male rats fed a diet with or without 2% di(2-ethylhexyl)phthalate (DEHP) for 12 days. 2. All enzyme activities were higher at alkaline than at neutral pH in both groups. 3. The effect of the DEHP-diet on the peroxisomal enzymes was different in kidney and liver. Acyl-CoA oxidase activity was raised three- and sixfold in kidney and liver homogenates, respectively. The activity of D-amino acid oxidase decrease in liver, but increased in kidney homogenates. In liver homogenates, urate oxidase activity was not affected by the DEHP diet. The catalase activity was twofold induced in liver, but not in kidney. 4. The differences suggest that the changes of peroxisomal enzyme activities by DEHP treatment are not directly related to peroxisome proliferation. 5. DEHP treatment caused a marked increase of total and peroxisomal fatty acid oxidation in rat liver homogenates. 6. In the control group the rate of peroxisomal fatty acid oxidation was higher at alkaline pH than at neutral pH. 7. This rate was equal at both pH values in the DEHP-fed group, in contrast to the acyl-CoA oxidase activity. These results indicate that after DEHP treatment other parameters than acyl-CoA oxidase activity become limiting for peroxisomal beta-oxidation.

Animals↗
PubMed1991

Immunochemical analysis of the peroxisomal beta-oxidation enzymes in rat and human heart and skeletal muscle and in skeletal muscle of Zellweger patients.

Immunoblot analyses with antibodies against the peroxisomal beta-oxidation enzymes from rat liver showed the presence of these enzymes in rat and human liver and kidney and rat adrenal gland. The bifunctional protein could not be detected in muscle tissues or cultured muscle cells. Acyl-CoA oxidase was detected in rat heart and cultured human muscle cells. 3-Ketoacyl-CoA thiolase was also detected in human and rat heart and skeletal muscle; however, this enzyme was not detectable in skeletal muscle of Zellweger patients, in agreement with the absence of peroxisomal fatty acid oxidation.

Acetyl-CoA C-Acyltransferase↗
PubMed1991

Disturbances of cerebral purine and pyrimidine metabolism in young children with chronic renal failure.

Chronic renal failure during childhood may be associated with delayed cognitive development. From 10 children with chronic renal failure, aged 2-59 months, plasma and cerebrospinal fluid (CSF) purines and pyrimidines have been determined. A marked increase of pseudouridine and cytidine was demonstrated in CSF of 10 and 8 children, respectively. The plasma concentration of pseudouridine was increased in a varying degree to a maximal value of more than 10 times the upper limit of normal. The plasma concentration of cytidine showed only moderately elevated values. In 3 children the study of CSF and plasma was repeated 6 weeks after the start of continuous ambulatory peritoneal dialysis. The abnormal concentrations of pseudouridine and cytidine were still present in CSF and plasma. Further studies are necessary to elucidate the cause of this unknown biochemical aberration of the central nervous system.

Cerebral Cortex↗
PubMed1990

The effect of di(ethylhexyl)phthalate on fatty acid oxidation and carnitine palmitoyltransferase in various rat tissues.

Male rats were fed a diet with or without 2% di(2-ethylhexyl)phthalate (DEHP) for 12 days. Total and peroxisomal oxidation rates of palmitic and arachidonic acid were increased in homogenates of liver and kidney after DEHP administration. The relative peroxisomal contribution to the total oxidation was only higher in liver. The activities of acyl-CoA oxidase and carnitine palmitoyltransferase were also higher in both tissues. Immunoblots showed that the increase of fatty acid oxidation was associated with a higher concentration of enzymes of peroxisomal and mitochondrial beta-oxidation. DEHP did not change total and peroxisomal fatty acid oxidation and activity of carnitine palmitoyltransferase of homogenates of heart and skeletal muscle. The cause for the tissue-specific response is discussed.

Animals↗
PubMed1990

The involvement of fatty acid binding protein in peroxisomal fatty acid oxidation.

Rat liver fatty acid-binding protein (FABP) can function as a fatty acid donor protein for both peroxisomal and mitochondrial fatty acid oxidation, since 14C-labeled palmitic acid bound to FABP is oxidized by both organelles. FABP is, however, not detected in peroxisomes and mitochondria of rat liver by ELISA. Acyl-CoA oxidase activity of isolated peroxisomes was not changed by addition of FABP or flavaspidic acid, an inhibitor of fatty acid binding to FABP, nor by disruption of the peroxisomal membranes. These data indicate that FABP may transfer fatty acids to peroxisomes, but is not involved in the transport of acyl-CoA through the peroxisomal membrane.

Acyl Coenzyme A↗