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Biomedical subjects

C Jakobs

Publications and source records attributed to C Jakobs.

At least 253 records · Page 14Linked to original sources
PubMed1992

Characteristics and subcellular localization of pristanoyl-CoA synthetase in rat liver.

We have investigated the activation of pristanic acid to its CoA-ester in rat liver. The results show that peroxisomes, mitochondria as well as microsomes contain pristanoyl-CoA synthetase activity. On the basis of competition experiments and immunoprecipitation studies using antibodies raised against rat liver microsomal long-chain fatty acyl-CoA synthetase (EC 6.2.1.3) we conclude that pristanic acid is activated by the same enzyme which activates long-chain fatty acids, i.e., long-chain fatty acyl-CoA synthetase.

Animals↗
PubMed1992

Identification of pristanoyl-CoA oxidase as a distinct, clofibrate non-inducible enzyme in rat liver peroxisomes.

In this paper we describe the identification of pristanoyl-CoA oxidase activity in rat liver peroxisomes. This activity was not stimulated by clofibrate feeding. Furthermore, the activity was found in multiple tissues. These results show that pristanoyl-CoA oxidase is different from any of the known oxidases which include a clofibrate-inducible acyl-CoA oxidase and the recently identified cholestanoyl-CoA oxidase. Gelfiltration and chromatofocusing experiments provide conclusive evidence that we are dealing with a novel acyl-CoA oxidase with a unique function in peroxisomal beta-oxidation.

Animals↗
PubMed1992

Analysis of pipecolic acid in biological fluids using capillary gas chromatography with electron-capture detection and [2H11]pipecolic acid as internal standard.

A sensitive and accurate stable isotope dilution assay was developed for the measurement of pipecolic acid in body fluids using capillary gas chromatography with electron-capture detection. The method utilizes [2H11]pipecolic acid as the internal standard. Sample preparation consisted of derivatization in aqueous solution (pH 11.5) of the amine moiety with methyl chloroformate to the N-methylcarbamate, followed by acidic ethyl acetate extraction at pH less than or equal to 2 and further derivatization of the carboxyl moiety with pentafluorobenzyl bromide, the excess of which was removed by solid-phase extraction. Control values have been determined in the plasma of at-term infants, age greater than 1 week (n = 21, mean = 1.36 microM, range = 0.47-3.27 microM). The utility of the method was demonstrated by quantitating pipecolic acid in biological fluids derived from patients with peroxisomal disorders. The method was validated against an established electron-capture negative ion mass fragmentographic technique.

Body Fluids↗
PubMed1992

Zellweger syndrome in a preterm, small for gestational age infant.

A preterm (gestational age 34 weeks), small for gestational age infant (birth weight less than P2,3) is described. Because of unexplained slightly disturbed liver function tests at age 2 months, extensive metabolic examinations were performed. Elevated blood levels of very long-chain fatty acids, pipecolic acid and abnormal levels of bile acid intermediates were detected, suggesting a peroxisomal disorder. The plasmalogen content of erythrocytes was decreased. Morphologically distinct peroxisomes were absent in the liver. In fibroblasts an accumulation of very long-chain fatty acids, decreased activity of acyl-CoA:dihydroxyacetone phosphate acyltransferase and impaired de novo biosynthesis of plasmalogens was found. In summary, a mild variant of the classical cerebro-hepato-renal syndrome of Zellweger was found without the characteristic clinical facial signs.

Bile Acids and Salts↗
PubMed1992

3-Methylglutaconic aciduria associated with Pearson syndrome and respiratory chain defects.

3-Methylglutaconic aciduria was detected in four patients with Pearson syndrome, a multitissue disorder with hematologic abnormalities, lactic acidosis resulting from defective oxidative phosphorylation, and deletions in the mitochondrial genome. 3-Methylglutaconic acid may be an additional useful marker for Pearson syndrome and may be a more specific marker than other organic acids identified in this disorder.

Acidosis, Lactic↗
PubMed1992

Familial hypotonia of childhood caused by isolated 3-methylcrotonyl-coenzyme A carboxylase deficiency.

Hypotonia was the initial symptom in four siblings from a nonconsanguineous Tunisian-Jewish family. Plasma carnitine was severely deficient, and urinary organic acid analysis revealed increased excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. 3-Methylcrotonyl-coenzyme A carboxylase activity was reduced in skin fibroblasts; pyruvate carboxylase and serum biotinidase activities were normal. We conclude that 3-methylcrotonyl-coenzyme A carboxylase deficiency should be added to the list of metabolic causes of familial hypotonia of childhood.

Carbon-Carbon Ligases↗
PubMed1992

In vivo study of phytanic acid alpha-oxidation in classic Refsum's disease and chondrodysplasia punctata.

A series of in vivo experiments is described in which [1-13C]phytanic acid was given as an oral substrate to a healthy subject and two patients showing an impairment in phytanic acid degradation, one with Refsum's disease and one with chondrodysplasia punctata. After intake of the substrate by the control in a dose of 20 mg/kg body weight, the production of 13CO2 was measured in exhaled breath air and the concomitant formation of labeled 2-hydroxyphytanic acid and of pristanic acid was demonstrated by plasma analysis. After application of a substrate dose of 1 mg/kg body weight to the control, no substantial amounts of 13CO2 were measured, whereas time-dependent analysis of labeled 2-hydroxyphytanic acid in plasma yielded a concentration curve superimposed upon the baseline value (0.2 mumol/L) of the unlabeled substance. Phytanic acid accumulated in plasma from the Refsum's disease patient [649 mumol/L, controls > 1 y (n = 100): < 10 mumol/L], whereas the pristanic acid concentration was within the control range [1.4 mumol/L, controls > 1 y (n = 100): < 3 mumol/L]. Low amounts of 2-hydroxyphytanic acid were found normally present [0.04 mumol/L, controls > 1 y (n = 11): < 0.2 mumol/L], and formation of labeled 2-hydroxyphytanic acid could not be demonstrated after ingestion of [1-13C]phytanic acid in a dose of 1 mg/kg body weight. In addition to phytanic acid accumulation (232 mumol/L), the chondrodysplasia punctata patient showed an elevated 2-hydroxyphytanic acid plasma concentration (0.4 mumol/L), whereas the plasma pristanic acid level was in the control range (0.7 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Pristanic acid and phytanic acid in plasma from patients with peroxisomal disorders: stable isotope dilution analysis with electron capture negative ion mass fragmentography.

A sensitive and selective stable isotope dilution method was developed for the accurate quantitation of pristanic acid and phytanic acid using electron capture negative ion mass fragmentography on pentafluorobenzyl derivatives. This technique allows detection of 1 pg of each compound and was applied to plasma from healthy controls and patients suffering from various peroxisomal disorders. The age-dependency of phytanic and pristanic acid levels in plasma from healthy controls was demonstrated. The involvement of peroxisomes in the beta-oxidation of pristanic acid was concluded from its accumulation in plasma from patients with peroxisomal deficiencies. Pristanic acid/phytanic acid ratios were markedly increased in bifunctional protein and/or 3-oxoacyl-CoA thiolase deficiency, indicating their role in the (differential) diagnosis of disorders of peroxisomal beta-oxidation.

Aging↗
PubMed1992

Phytanic acid alpha-oxidation: accumulation of 2-hydroxyphytanic acid and absence of 2-oxophytanic acid in plasma from patients with peroxisomal disorders.

A stable isotope dilution method was developed for the measurement of 2-hydroxyphytanic acid and 2-oxophytanic acid in plasma. In plasma from healthy individuals and from patients with Refsum's disease, 2-hydroxyphytanic acid was found at levels less than 0.2 mumol/l, whereas the acid accumulated in plasma from patients with rhizomelic chondrodysplasia punctata, generalized peroxisomal dysfunction, and a single peroxisomal beta-oxidation enzyme deficiency. In plasma from both healthy controls and patients with peroxisomal disorders, 2-oxophytanic acid was undetectable. Four different groups of diseases were characterized with a defective phytanic acid alpha-oxidation and/or pristanic acid beta-oxidation: 1) Refsum's disease, with a defect at phytanic acid alpha-hydroxylation; 2) rhizomelic chondrodysplasia punctata, with a defect at 2-hydroxyphytanic acid decarboxylation; 3) generalized peroxisomal disorders, with defects at 2-hydroxyphytanic acid decarboxylation and at pristanic acid beta-oxidation; 4) single peroxisomal beta-oxidation enzyme deficiencies, with a defect at pristanic acid beta-oxidation, resulting in an impaired phytanic acid alpha-oxidation by inhibition. The results indicate that 2-hydroxyphytanic acid decarboxylation and pristanic acid beta-oxidation take place in peroxisomes.

Adolescent↗
PubMed1991

Stable isotope dilution analysis of N-acetylaspartic acid in CSF, blood, urine and amniotic fluid: accurate postnatal diagnosis and the potential for prenatal diagnosis of Canavan disease.

A sensitive and selective analytical technique is described for the determination of N-acetylaspartic acid in body fluids using stable isotope dilution in combination with positive chemical ionization mass spectrometry with selected ion monitoring. Control mean and ranges have been established: in urine 19.5 and 6.6-35.4 mumol/mmol creat.; in plasma 0.44 and 0.17-0.81 mumol/L; in cerebrospinal fluid 1.51 and 0.25-2.83 mumol/L; and in amniotic fluid 1.27 and 0.30-2.55 mumol/L. In a patient with Canavan disease, N-acetylaspartic acid concentration was elevated 80-fold in urine and 20-fold in plasma compared to the control means. A subsequent pregnancy of the mother was monitored and the N-acetylaspartic acid concentration in the amniotic fluid was within the control range and a healthy child was born.

Amidohydrolases↗