Biomedical subjects

C Jakobs

Publications and source records attributed to C Jakobs.

329 records · Page 19Linked to original sources

PubMedDate not supplied

Multiple syndromes of 3-methylglutaconic aciduria.

The most common clinical syndromes associated with 3-methylglutaconic aciduria are presented. In some patients these syndromes are multisystemic, progressive disorders of unknown etiology. Tissues deriving significant energy through oxidative metabolism (notably brain and cardiac muscle) are most often affected and in some the primary defect may reside within the mitochondrial respiratory chain. Although increasing biochemical evidence suggests that 3-methylglutaconic aciduria may correlate with deranged mitochondrial energy metabolism, the biochemical origin of 3-methylglutaconic acid and the significance of its increased excretion remain unknown. This review describes these syndromes and illustrates the necessity of urinary organic acid analysis to assist in the differential diagnosis.

Brain Diseases, Metabolic↗

PubMedDate not supplied

Hyperoxia-induced clonogenic killing of HeLa cells associated with respiratory failure and selective inactivation of Krebs cycle enzymes.

Cellular intoxication by elevated concentrations of O2 may be considered as a model for accelerated cellular aging processes resulting from excessive free radical production by normal metabolic pathways. We describe here that exposure of HeLa cell cultures to 80% O2 for 2 days causes progressive growth inhibition and loss of reproductive capacity. This intoxication was correlated with inhibition of cellular O2 consumption and inactivation of 3 mitochondrial flavoproteins, i.e., partial inactivation of NADH and succinate dehydrogenases and total inactivation of alpha-ketoglutarate dehydrogenase. As alpha-ketoglutarate dehydrogenase controls the influx of glutamine/glutamate into the Krebs cycle, which is the major pathway for oxidative ATP generation in HeLa cells, the inactivation of alpha-ketoglutarate dehydrogenase was expectedly correlated with a net fall in glutamine/glutamate utilization. Furthermore, a simultaneous increase in glucose consumption and lactate production was observed, indicating that the cellular response to respiratory failure is to generate more ATP from glycolysis. In spite of this response, extensive depletion of ATP was observed. Thus, hyperoxia-induced growth inhibition and loss of clonogenicity seem to be due primarily to an impairment of mitochondrial energy metabolism resulting from inactivation of SH-group-containing flavoprotein enzymes localized at or near the inner mitochondrial membrane. These observations may be relevant for theories implicating loss of mitochondrial function as a prime factor in the aging process.

Adenosine Triphosphate↗

PubMedDate not supplied

[L-2-hydroxyglutaric aciduria -- a rare cause of macrocephaly].

We report on a 9-year-old girl who was referred to our department because of increasing macrocephaly and school problems. The neurological examination disclosed mild cerebellar dysfunction and positive pyramidal tract signs. An MRI of the brain revealed extensive signal alterations of the white matter. Biochemical investigations established the diagnosis of L-2-hydroxyglutaric aciduria which has to be kept in mind as a rare cause of macrocephaly.

Adolescent↗

PubMedDate not supplied

Differential distribution of apolipoprotein E isoforms in human plasma lipoproteins.

The polymorphism of apolipoprotein E (apo E) accounts for a substantial amount of the genetic variance of cholesterol levels in man. The epsilon-2 allele and the epsilon-4 allele raises plasma and low density lipoprotein cholesterol levels as compared to the epsilon-3 allele. Whereas the lower cholesterol levels in carriers of the epsilon-2 allele can, at least in part, be attributed to the grossly deficient binding of apo E-2 to the apo B,E receptor, apo E-3 and E-4 bind to the same degree. We used gel filtration and ultracentrifugation to separate lipoproteins and subsequent immunoblotting analysis to study the apo E isoform distribution. We always found lipoproteins of lower density relatively enriched in apo E-4 and high density lipoproteins relatively depleted of apo E-4 as compared to apo E-3. This was also seen in plasma of heterozygous subjects that simultaneously express two apo E isoforms. Also, the apo E-A-II complex was directly shown by immunoblotting. Furthermore, when purified iodinated apo E was incubated with plasma in vitro, apo E-4 also reassociated more with lipoproteins of lower density than apo E-3. We conclude that apo E-3 and apo E-4 have a different lipoprotein particle distribution in vivo. This differential lipoprotein distribution may account for differences in the metabolism between apo E-3 and E-4.

Apolipoprotein E2↗

PubMedDate not supplied

Fat elimination in parenterally fed low birth weight infants during the first two weeks of life.

Eighteen low birth weight infants (27-34 wk gestation) were given supplementary parenteral nutrition via peripheral veins of a maximal dose of 8.5 g glucose, 2.5 g amino acids (Aminovenös päd 10%) and 2 g soybean oil egg lecithin emulsion (Intralipid 10%) kg body weight/24 hr. The fat emulsion was infused continuously at a rate of 0.084 g/kg body weight/hr. The elimination of Intralipid from the blood stream was controlled by enzymatic determination of serum triglyceride concentrations, and the fatty acid pattern of the serum lipids was determined by gas chromatography. The serum triglyceride concentrations were 0.60 +/- 0.16 mmol/liter on the 1st day, increased to 0.96 +/- 0.29 mmol/liter up to the 5th day, and approached a level around 0.90 mmol/liter in the further course. No hypertriglyceridemia was noted. The fatty acid pattern of the serum lipids showed a linoleic acid fraction of 8.1 +/- 4.0% in the beginning, which was followed by a continuous increase up to 27.8 +/- 4.8% on the 7th day. No significant changes were noticed thereafter. The levels were within the normal limits as found in 2-wk-old enterally fed preterm infants of comparative maturity (25.6 +/- 3.4%). We conclude that the preterm infants can eliminate Intralipid from the blood stream if maximal dosage and infusion rate, as described above, are applied.

Fat Emulsions, Intravenous↗