Krebs acids
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- MeSH
- biochemie MeSH
- citrátový cyklus MeSH
- fyziologie MeSH
- koenzym A MeSH
- Publikační typ
- biografie MeSH
- MeSH
- arginin biosyntéza fyziologie MeSH
- biochemické jevy MeSH
- lidé MeSH
- močovina * dějiny metabolismus MeSH
- ornithin biosyntéza fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- historické články MeSH
- O autorovi
- Krebs, Hans Adolf, 1900-1981 Autorita
Methyltriphenylphosphonium (TPMP) salts have been widely used to measure the mitochondrial membrane potential and the triphenylphosphonium (TPP+) moiety has been attached to many bioactive compounds including antioxidants to target them into mitochondria thanks to their high affinity to accumulate in the mitochondrial matrix. The adverse effects of these compounds on cellular metabolism have been insufficiently studied and are still poorly understood. Micromolar concentrations of TPMP cause a progressive inhibition of cellular respiration in adherent cells without a marked effect on mitochondrial coupling. In permeabilized cells the inhibition was limited to NADH-linked respiration. We found a mixed inhibition of the Krebs cycle enzyme 2-oxoglutarate dehydrogenase complex (OGDHC) with an estimated IC50 3.93 [3.70-4.17] mM, which is pharmacologically plausible since it corresponds to micromolar extracellular concentrations. Increasing the lipophilic character of the used TPP+ compound further potentiates the inhibition of OGDHC activity. This effect of TPMP on the Krebs cycle ought to be taken into account when interpreting observations on cells and mitochondria in the presence of TPP+ derivatives. Compounds based on or similar to TPP+ derivatives may also be used to alter OGDHC activity for experimental or therapeutic purposes.
- MeSH
- buněčné linie MeSH
- citrátový cyklus účinky léků MeSH
- citrátsynthasa účinky léků metabolismus MeSH
- glutamátdehydrogenasa účinky léků metabolismus MeSH
- isocitrátdehydrogenasa účinky léků metabolismus MeSH
- ketoglutarátdehydrogenasový komplex antagonisté a inhibitory metabolismus MeSH
- kosterní svaly enzymologie MeSH
- krysa rodu rattus MeSH
- malátdehydrogenasa účinky léků metabolismus MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- oniové sloučeniny farmakologie MeSH
- potkani Wistar MeSH
- pyruvátdehydrogenasový komplex účinky léků metabolismus MeSH
- svalové mitochondrie účinky léků enzymologie MeSH
- tritylové sloučeniny farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Psychosis is a state of altered thoughts which often accompanies schizophrenia. It was suggested that changes in energetic metabolism accompany psychosis and post-psychosis states. Here, we use the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to experimentally induce psychosis-like behavior in rats. We addressed an effect of single and repeated (5×) MK-801 application (0.3 mg/kg; i.p.) on the energy metabolism in homogenates and crude mitochondrial fraction (CMF) of the striatum (STR), prefrontal cortex (PFC), and the hippocampus (HIP) of the adult male Wistar rat (n = 39). In each brain region, we assessed activity of glycolytic (hexokinase (HK) and lactate dehydrogenase (LDH)) and Krebs cycle enzymes (citrate synthase (CS) and malate dehydrogenase (MDH)) 2 h and 3 days (3d) after the last MK-801 application together with relative respiratory rates assessment in tissue homogenate. In STR, a single MK-801 application led to a decrease in the LDH (p = 0.0035) and the increase of the MDH (p = 0.0043) activities following 3d. Therein, repeated MK-801 doses evoked increased LDH (p = 0.0204) and CS (p = 0.0019) activities in the homogenate 2 h and increased HK (p = 0.0007) 3d after the last application. Elevated HK activity within CMF was observed after 3d (p = 0.0054). In PFC, repeated MK-801 application decreased HK activity in the homogenate 3d after the final application (p = 0.0234). Correspondingly, PFC HK activity in CMF of repeated administration samples dropped (p = 0.003). In HIP, repeated MK-801 administration led to increased respiration of SDH (p = 0.0475) only 2 h after the last application and decreased CS activity (p = 0.0160) was observed 3d after the last application. Our results indicate a progressive metabolic dysregulation of glycolytic and Krebs cycle enzymes following repeated inhibition of NMDA receptors activity in a region-specific manner. Energetic alterations may form a basis for persisting cognitive problems during and following a psychosis in schizophrenia patients.
- MeSH
- citrátový cyklus MeSH
- citrátsynthasa metabolismus farmakologie MeSH
- dizocilpinmaleát * farmakologie MeSH
- hexokinasa metabolismus farmakologie MeSH
- hipokampus MeSH
- krysa rodu rattus MeSH
- L-laktátdehydrogenasa metabolismus MeSH
- lidé MeSH
- N-methylaspartát * farmakologie MeSH
- potkani Wistar MeSH
- prefrontální mozková kůra MeSH
- receptory N-methyl-D-aspartátu metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Obstructive sleep apnea syndrome, characterized by repetitive episodes of tissue hypoxia, is associated with several metabolic impairments. Role of fatty acids and lipids attracts attention in its pathogenesis for their metabolic effects. Parallelly, hypoxia-induced activation of reverse tricarboxylic acid cycle (rTCA) with reductive glutamine metabolism provides precursor molecules for de novo lipogenesis. Gas-permeable cultureware was used to culture L6-myotubes in chronic hypoxia (12%, 4% and 1% O2) with 13C labelled glutamine and inhibitors of glutamine uptake or rTCA-mediated lipogenesis. We investigated changes in lipidomic profile, 13C appearance in rTCA-related metabolites, gene and protein expression of rTCA-related proteins and glutamine transporters, glucose uptake and lactate production. Lipid content increased by 308% at 1% O2, predominantly composed of saturated fatty acids, while triacylglyceroles containing unsaturated fatty acids and membrane lipids (phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositol) decreased by 20-70%. rTCA labelling of malate, citrate and 2-hydroxyglutarate increased by 4.7-fold, 2.2-fold and 1.9-fold in 1% O2, respectively. ATP-dependent citrate lyase inhibition in 1% O2 decreased lipid amount by 23% and increased intensity of triacylglyceroles containing unsaturated fatty acids by 56-80%. Lactate production increased with hypoxia. Glucose uptake dropped by 75% with progression of hypoxia from 4% to 1% O2. Protein expression remained unchanged. Altogether, hypoxia modified cell metabolism leading to lipid composition alteration and rTCA activation.
The aim was to determine the effects of enhanced availability of branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) on ammonia detoxification to glutamine (GLN) and protein metabolism in two types of skeletal muscle under hyperammonemic conditions. Isolated soleus (SOL, slow-twitch) and extensor digitorum longus (EDL, fast-twitch) muscles from the left leg of white rats were incubated in a medium with 1 mM ammonia (NH3 group), BCAAs at four times the concentration of the controls (BCAA group) or high levels of both ammonia and BCAA (NH3 + BCAA group). The muscles from the right leg were incubated in basal medium and served as paired controls. L-[1-14C]leucine was used to estimate protein synthesis and leucine oxidation, and 3-methylhistidine release was used to evaluate myofibrillar protein breakdown. We observed decreased protein synthesis and glutamate and α-ketoglutarate (α-KG) levels and increased leucine oxidation, GLN levels, and GLN release into medium in muscles in NH3 group. Increased leucine oxidation, release of branched-chain keto acids and GLN into incubation medium, and protein synthesis in EDL were observed in muscles in the BCAA group. The addition of BCAAs to medium eliminated the adverse effects of ammonia on protein synthesis and adjusted the decrease in α-KG found in the NH3 group. We conclude that (i) high levels of ammonia impair protein synthesis, activate BCAA catabolism, enhance GLN synthesis, and decrease glutamate and α-KG levels and (ii) increased BCAA availability enhances GLN release from muscles and attenuates the adverse effects of ammonia on protein synthesis and decrease in α-KG.
- MeSH
- amoniak otrava MeSH
- citrátový cyklus účinky léků MeSH
- glutamin agonisté metabolismus MeSH
- hyperamonemie enzymologie metabolismus patofyziologie MeSH
- jaterní cirhóza etiologie metabolismus MeSH
- kyseliny ketoglutarové metabolismus MeSH
- methylhistidiny metabolismus MeSH
- orgánová specificita MeSH
- osmolární koncentrace MeSH
- oxidace-redukce MeSH
- potkani Wistar MeSH
- proteolýza účinky léků MeSH
- proteosyntéza účinky léků MeSH
- radioizotopy uhlíku MeSH
- svalová vlákna typu I účinky léků enzymologie metabolismus MeSH
- svalová vlákna typu II účinky léků enzymologie metabolismus MeSH
- svalové proteiny genetika metabolismus MeSH
- techniky in vitro MeSH
- větvené aminokyseliny metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
BACKGROUND: Omega-3 (n-3) fatty acids (FA) play and important role in neural development and other metabolic diseases such as obesity and diabetes. The knowledge about the in vivo content and distribution of n-3 FA in human body tissues is not well established and the standard quantification of FA is invasive and costly. PURPOSE: To detect omega-3 (n-3 CH3 ) and non-omega-3 (CH3 ) methyl group resonance lines with echo times up to 1200 msec, in oils, for the assessment of n-3 FA content, and the n-3 FA fraction in adipose tissue in vivo. STUDY TYPE: Prospective technical development. POPULATION: Three oils with different n-3 FA content and 24 healthy subjects. FIELD STRENGTH/SEQUENCE: Single-voxel MR spectroscopy (SVS) with a point-resolved spectroscopy (PRESS) sequence with an echo time (TE) of 1000 msec at 7 T. ASSESSMENT: Knowledge about the J-coupling evolution of both CH3 resonances was used for the optimal detection of the n-3 CH3 resonance line at a TE of 1000 msec. The accuracy of the method in oils and in vivo was validated from a biopsy sample with gas chromatography analysis. STATISTICAL TESTS: SVS data were compared to gas chromatography with the Pearson correlation coefficient. RESULTS: T2 relaxation times in oils were assessed as follows: CH2 , 65 ± 22 msec; CH3 , 325 ± 7 msec; and n-3 CH3 , 628 ± 34 msec. The n-3 FA fractions from oil phantom experiments (n = 3) were in agreement with chromatography analysis and the comparison of in vivo obtained data with the results of chromatography analysis (n = 5) yielded a significant correlation (P = 0.029). DATA CONCLUSION: PRESS with ultralong-TE can detect and quantify the n-3 CH3 signal in vivo at 7 T. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:71-82.
- MeSH
- dospělí MeSH
- fantomy radiodiagnostické MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie * MeSH
- omega-3 mastné kyseliny chemie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- počítačová simulace MeSH
- podkožní tuk diagnostické zobrazování MeSH
- poměr signál - šum MeSH
- prospektivní studie MeSH
- senioři MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
