Studies on the metabolism of glycolyl-CoA

1990 ◽  
Vol 68 (5) ◽  
pp. 846-851 ◽  
Author(s):  
Joseph Vamecq ◽  
Jacques H. Poupaert
Keyword(s):  
Rat Liver ◽  
Pyruvate Dehydrogenase ◽  
Citrate Synthase ◽  
Rat Kidney ◽  
Kidney Cortex ◽  
Rat Liver Mitochondria ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Rat Kidney Cortex ◽  
Semialdehyde Dehydrogenase

Glycolyl-CoA can be formed during the course of the β-oxidation by rat liver mitochondria of 4-hydroxybutyrate. The existence of this β-oxidation has been previously supported by the occurrence of 4-hydroxybutyrate and its β-oxidation catabolites in urine from patients with 4-hydroxybutyric aciduria, an inborn error of γ-aminobutyric acid metabolism due to the deficiency of succinic semialdehyde dehydrogenase. The characteristics of the mitochondrial β-oxidation of 4-hydroxybutyrate were, in rat liver, compared with those of the mitochondrial β-oxidation of butyrate. The inhibition by malonate of the oxidation of 4-hydroxybutyrate was about twofold weaker than that of oxidation of butyrate, whereas both oxidations were abolished by preincubating the mitochondria with 1 mM valproic acid, a known inhibitor of mitochondrial β-oxidation. Mitochondria from rat kidney cortex were demonstrated to catalyse, as previously shown for hepatic mitochondria, the carnitine-dependent oxidation of 12-hydroxylauroyl-CoA. ω-Hydroxymonocarboxylyl-CoAs are thus concluded to be precursors of glycolyl-CoA also in rat kidney cortex. In addition, 3-hydroxypyruvate was found to be a precursor of glycolyl-CoA, since it was oxidized by bovine heart pyruvate dehydrogenase with a cofactor requirement similar to that of pyruvate oxidation. Glycolyl-CoA was a substrate of carnitine acetyltransferase (pigeon breast muscle). Pig heart citrate synthase was capable of catalyzing the condensation of glycolyl-CoA with oxaloacetate. The product of this reaction induced low NADH production rates dependent on the addition of porcine heart aconitase and isocitrate dehydrogenase.Key words: glycolyl-CoA, ω-hydroxymonocarboxylates, β-oxidation, 4-hydroxybutyrate, CoA-dependent 3-hydroxypyruvate oxidation, pyruvate dehydrogenase, citrate synthase, hydroxy citrate.

scholarly journals DIRECT COUNTING AND SIZING OF MITOCHONDRIA IN SOLUTION

1972 ◽  
Vol 54 (2) ◽  
pp. 325-345 ◽  
Author(s):  
Adrian R. L. Gear ◽  
Jana M. Bednarek
Keyword(s):  
Electron Microscopy ◽  
Rat Liver ◽  
Rat Kidney ◽  
Mitochondrial Protein ◽  
Kidney Cortex ◽  
Rat Liver Mitochondria ◽  
Particle Volume ◽  
Drug Induced ◽  
Rat Kidney Cortex ◽  
The Mean

Resistive particle counting has been developed for the accurate sizing and counting of mitochondria in solution. The normal detection limit with a 30 µ aperture is 0.48 µ diameter, or 0.056 µ3 particle volume The mean volume of rat liver mitochondria was 0.42 µ3 or 0.93 µ in diameter. The average value for numbers of particles per milligram of mitochondrial protein was 4.3 x 103, and per gram of rat liver was about 11 x 1010. These values compare satisfactorily with those derived by light microscopy and electron microscopy. The mean volume for mitochondria from rat heart was 0 60 µ3 and from rat kidney cortex, 0.23 µ3. These values agree within 15% of those determined by electron microscopy of whole tissue. Mitochondrial fragility and contaminating subcellular organelles were shown to have little influence on the experimentally determined size distributions The technique may be applied to rapid swelling studies, as well as to estimations of the number and size of mitochondria from animals under different conditions such as liver regeneration and hormonal, pathological, or drug-induced states Mitochondrial DNA, RNA, cytochrome c-oxidase, cytochrome (a ÷ a3), and iron were nearly constant per particle over large differences in particle size. Such data may be particularly valuable for biogenesis studies and support the hypothesis that the net amount per particle of certain mitochondrial constituents remains constant during mitochondrial growth and enlargement

scholarly journals Carbohydrate metabolism of the perfused rat liver

1967 ◽  
Vol 105 (2) ◽  
pp. 869-875 ◽  
Author(s):  
B. D. Ross ◽  
R. Hems ◽  
R. A. Freedland ◽  
H. A. Krebs
Keyword(s):  
Rat Liver ◽  
Rat Kidney ◽  
Kidney Cortex ◽  
Additive Effects ◽  
Perfusion Medium ◽  
Rat Kidney Cortex ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate ◽  
Glycogen Stores ◽  
Glucose Formation

1. The rates of gluconeogenesis from most substrates tested in the perfused livers of well-fed rats were about half of those obtained in the livers of starved rats. There was no difference for glycerol. 2. A diet low in carbohydrate increased the rates of gluconeogenesis from some substrates but not from all. In general the effects of a low-carbohydrate diet on rat liver are less marked than those on rat kidney cortex. 3. Glycogen was deposited in the livers of starved rats when the perfusion medium contained about 10mm-glucose. The shedding of glucose from the glycogen stores by the well-fed liver was greatly diminished by 10mm-glucose and stopped by 13·3mm-glucose. Livers of well-fed rats that were depleted of their glycogen stores by treatment with phlorrhizin and glucagon synthesized glycogen from glucose. 4. When two gluconeogenic substrates were added to the perfusion medium additive effects occurred only when glycerol was one of the substrates. Lactate and glycerol gave more than additive effects owing to an increased rate of glucose formation from glycerol. 5. Pyruvate also accelerated the conversion of glycerol into glucose, and the accelerating effect of lactate can be attributed to a rapid formation of pyruvate from lactate. 6. Butyrate and oleate at 2mm, which alone are not gluconeogenic, increased the rate of gluconeogenesis from lactate. 7. The acceleration of gluconeogenesis from lactate by glucagon was also found when gluconeogenesis from lactate was stimulated by butyrate and oleate. This finding is not compatible with the view that the primary action of glucagon in promoting gluconeogenesis is an acceleration of lipolysis. 8. The rate of gluconeogenesis from pyruvate at 10mm was only 70% of that at 5mm. This ‘inhibition’ was abolished by oleate or glucagon.

scholarly journals Succinic Semialdehyde Dehydrogenase Deficiency: Review of the Natural History Study

2021 ◽  
pp. 088307382098126
Author(s):  
Phillip L. Pearl ◽  
Melissa L. DiBacco ◽  
Christos Papadelis ◽  
Thomas Opladen ◽  
Ellen Hanson ◽  
...  
Keyword(s):  
Natural History ◽  
Psychiatric Symptoms ◽  
Epileptiform Activity ◽  
Laboratory Data ◽  
Standard Of Care ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Natural History Study ◽  
Semialdehyde Dehydrogenase ◽  
Verbal Score

Objective: The SSADHD Natural History Study was initiated in 2019 to define the natural course and identify biomarkers correlating with severity. Methods: The study is conducted by 4 institutions: BCH (US clinical), WSU (bioanalytical core), USF (biostatistical core), and Heidelberg (iNTD), with support from the family advocacy group (SSADH Association). Recruitment goals were to study 20 patients on-site at BCH, 10 with iNTD, and 25 as a standard-of care cohort. Results: At this half-way point of this longitudinal study, 28 subjects have been recruited (57% female, mean 9 years, range 18 months–40 years). Epilepsy is present in half and increases in incidence and severity, as do psychiatric symptoms, in adolescence and adulthood. The average Full Scale IQ (FSIQ) was 53 (Verbal score of 56, Non Verbal score of 49), and half scored as having ASD. Although there was no correlation between gene variant and phenotypic severity, there were extreme cases of lowest functioning in one individual and highest in another that may have genotype-phenotype correlation. The most common EEG finding was mild background slowing with rare epileptiform activity, whereas high-density EEG and magnetoencephalography showed reduction in the gamma frequency band consistent with GABAergic dysfunction. MR spectroscopy showed elevations in the GABA/NAA ratio in all regions studied with no crossover between subjects and controls. Conclusions: The SSADH Natural History Study is providing a unique opportunity to study the complex pathophysiology longitudinally and derive electrophysiologic, neuroimaging, and laboratory data for correlation and to serve as biomarkers for clinical trials and prognostic assessments in this ultra-rare inherited disorder of GABA metabolism.

scholarly journals Postmortem Analyses in a Patient With Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD): II. Histological, Lipid, and Gene Expression Outcomes in Regional Brain Tissue

2021 ◽  
pp. 088307382098774
Author(s):  
Dana C. Walters ◽  
Regan Lawrence ◽  
Trevor Kirby ◽  
Jared T. Ahrendsen ◽  
Matthew P. Anderson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dehydrogenase Deficiency ◽  
Metabotropic Glutamate Receptor ◽  
Total Phospholipid ◽  
Null Mouse ◽  
Succinic Semialdehyde ◽  
Long Term Effects ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Succinic Semialdehyde Dehydrogenase Deficiency

This study has extended previous metabolic measures in postmortem tissues (frontal and parietal lobes, pons, cerebellum, hippocampus, and cerebral cortex) obtained from a 37-year-old male patient with succinic semialdehyde dehydrogenase deficiency (SSADHD) who expired from SUDEP (sudden unexplained death in epilepsy). Histopathologic characterization of fixed cortex and hippocampus revealed mild to moderate astrogliosis, especially in white matter. Analysis of total phospholipid mass in all sections of the patient revealed a 61% increase in cortex and 51% decrease in hippocampus as compared to (n = 2-4) approximately age-matched controls. Examination of mass and molar composition of major phospholipid classes showed decreases in phospholipids enriched in myelin, such as phosphatidylserine, sphingomyelin, and ethanolamine plasmalogen. Evaluation of gene expression (RT2 Profiler PCR Arrays, GABA, glutamate; Qiagen) revealed dysregulation in 14/15 GABAA receptor subunits in cerebellum, parietal, and frontal lobes with the most significant downregulation in ∊, θ, ρ1, and ρ2 subunits (7.7-9.9-fold). GABAB receptor subunits were largely unaffected, as were ionotropic glutamate receptors. The metabotropic glutamate receptor 6 was consistently downregulated (maximum 5.9-fold) as was the neurotransmitter transporter (GABA), member 13 (maximum 7.3-fold). For other genes, consistent dysregulation was seen for interleukin 1β (maximum downregulation 9.9-fold) and synuclein α (maximal upregulation 6.5-fold). Our data provide unique insight into SSADHD brain function, confirming astrogliosis and lipid abnormalities previously observed in the null mouse model while highlighting long-term effects on GABAergic/glutamatergic gene expression in this disorder.

scholarly journals Magnetic Resonance Imaging (MRI) and Spectroscopy in Succinic Semialdehyde Dehydrogenase Deficiency

2021 ◽  
pp. 088307382199129
Author(s):  
Onur Afacan ◽  
Edward Yang ◽  
Alexander P. Lin ◽  
Eduardo Coello ◽  
Melissa L. DiBacco ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Mr Spectroscopy ◽  
Succinic Semialdehyde ◽  
Resonance Imaging ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Semialdehyde Dehydrogenase ◽  
Magnetic Resonance Imaging Mri ◽  
Brain Gaba ◽  
Ssadh Deficiency

Succinic semialdehyde dehydrogenase (SSADH) deficiency is an autosomal recessive disorder of γ-aminobutyric acid (GABA) degradation, resulting in elevations of brain GABA and γ-hydroxybutyric acid (GHB). Previous magnetic resonance (MR) spectroscopy studies have shown increased levels of Glx in SSADH deficiency patients. Here in this work, we measure brain GABA in a large cohort of SSADH deficiency patients using advanced MR spectroscopy techniques that allow separation of GABA from overlapping metabolite peaks. We observed significant increases in GABA concentrations in SSADH deficiency patients for all 3 brain regions that were evaluated. Although GABA levels were higher in all 3 regions, each region had different patterns in terms of GABA changes with respect to age. We also report results from structural magnetic resonance imaging (MRI) of the same cohort compared with age-matched controls. We consistently observed signal hyperintensities in globus pallidus and cerebellar dentate nucleus.

scholarly journals Increase of Na/Pi-cotransport encoding mRNA in response to low Pi diet in rat kidney cortex.

1994 ◽  
Vol 269 (9) ◽  
pp. 6637-6639
Author(s):  
A. Werner ◽  
S.A. Kempson ◽  
J. Biber ◽  
H. Murer
Keyword(s):  
Rat Kidney ◽  
Kidney Cortex ◽  
Rat Kidney Cortex
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