Balanced bacterial metabolism is essential for cell homeostasis and growth and can be impacted by various stress factors. In particular, bacteria exposed to metals, including the nanoparticle form, can significantly alter their metabolic processes. It is known that the extensive and intensive use of food and feed supplements, including zinc, in human and animal nutrition alters the intestinal microbiota and this may negatively impact the health of the host. This study examines the effects of zinc (zinc oxide and zinc oxide nanoparticles) on key metabolic pathways of Escherichia coli. Transcriptomic and proteomic analyses along with quantification of intermediates of tricarboxylic acid (TCA) were employed to monitor and study the bacterial responses. Multi-omics analysis revealed that extended zinc exposure induced mainly oxidative stress and elevated expression/production of enzymes of carbohydrate metabolism, especially enzymes for synthesis of trehalose. After the zinc withdrawal, E. coli metabolism returned to a baseline state. These findings shed light on the alteration of TCA and on importance of trehalose synthesis in metal-induced stress and its broader implications for bacterial metabolism and defense and consequently for the balance and health of the human and animal microbiome.

• Klíčová slova
• Carbohydrate metabolism, Nanoparticles, Proteome, Transcriptome, Trehalose synthesis, Tricarboxylic acid cycle, Virulence, Zinc, Zinc oxide,
• MeSH
• citrátový cyklus * účinky léků   MeSH
• Escherichia coli * metabolismus   genetika   účinky léků   MeSH
• fyziologická adaptace MeSH
• metabolické sítě a dráhy účinky léků   MeSH
• oxid zinečnatý metabolismus   farmakologie   MeSH
• oxidační stres MeSH
• proteiny z Escherichia coli metabolismus   genetika   MeSH
• proteomika MeSH
• regulace genové exprese u bakterií účinky léků   MeSH
• stanovení celkové genové exprese MeSH
• transkriptom MeSH
• trehalosa * metabolismus   MeSH
• zinek * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• oxid zinečnatý MeSH
• proteiny z Escherichia coli MeSH
• trehalosa * MeSH
• zinek * 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.

• Klíčová slova
• L6 myotubes, glutamin, hypoxia, lipids, obstructive sleep apnea, reverse TCA,
• MeSH
• citrátový cyklus * genetika   MeSH
• hypoxie metabolismus   MeSH
• kosterní svalová vlákna metabolismus   MeSH
• lidé MeSH
• mastné kyseliny * metabolismus   MeSH
• nenasycené mastné kyseliny metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mastné kyseliny * MeSH
• nenasycené mastné kyseliny MeSH

Alterations in tricarboxylic acid (TCA) cycle metabolism are associated with hepatic metabolic disorders. Elevated hepatic acetate concentrations, often attributed to high caloric intake, are recognized as a pivotal factor in the etiology of obesity and metabolic syndrome. Therefore, the assessment of acetate breakdown and TCA cycle activity plays a central role in understanding the impact of diet-induced alterations on liver metabolism. Magnetic resonance-based deuterium metabolic imaging (DMI) could help to unravel the underlying mechanisms involved in disease development and progression, however, the application of conventional deuterated glucose does not lead to substantial enrichment in hepatic glutamine and glutamate. This study aimed to demonstrate the feasibility of DMI for tracking deuterated acetate breakdown via the TCA cycle in lean and diet-induced fatty liver (FL) rats using 3D DMI after an intraperitoneal infusion of sodium acetate-d3 at 9.4T. Localized and nonlocalized liver spectra acquired at 10 time points post-injection over a 130-min study revealed similar intrahepatic acetate uptake in both animal groups (AUCFL = 717.9 ± 131.1 mM▯min-1, AUClean = 605.1 ± 119.9 mM▯min-1, p = 0.62). Metabolic breakdown could be observed in both groups with an emerging glutamine/glutamate (Glx) peak as a downstream metabolic product (AUCFL = 113.6 ± 23.8 mM▯min-1, AUClean = 136.7 ± 41.7 mM▯min-1, p = 0.68). This study showed the viability of DMI for tracking substrate flux through the TCA cycle, underscoring its methodological potential for imaging metabolic processes in the body.

• Klíčová slova
• MASLD, TCA cycle, acetate, deuterium metabolic imaging, fatty liver disease, metabolism,
• MeSH
• acetáty metabolismus   MeSH
• analýza metabolického toku MeSH
• citrátový cyklus * MeSH
• deuterium * MeSH
• játra * metabolismus   diagnostické zobrazování   MeSH
• krysa rodu Rattus MeSH
• magnetická rezonanční tomografie MeSH
• potkani Sprague-Dawley MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetáty MeSH
• deuterium * MeSH

• Klíčová slova
• ARTERIOSCLEROSIS/metabolism *, TISSUE METABOLISM *,
• MeSH
• arterioskleróza metabolismus   MeSH
• ateroskleróza * MeSH
• citrátový cyklus * MeSH
• metabolismus * MeSH
• Publikační typ
• časopisecké články MeSH

Glycolytic shift is a characteristic feature of rapidly proliferating cells, such as cells during development and during immune response or cancer cells, as well as of stem cells. It results in increased glycolysis uncoupled from mitochondrial respiration, also known as the Warburg effect. Notch signalling is active in contexts where cells undergo glycolytic shift. We decided to test whether metabolic genes are direct transcriptional targets of Notch signalling and whether upregulation of metabolic genes can help Notch to induce tissue growth under physiological conditions and in conditions of Notch-induced hyperplasia. We show that genes mediating cellular metabolic changes towards the Warburg effect are direct transcriptional targets of Notch signalling. They include genes encoding proteins involved in glucose uptake, glycolysis, lactate to pyruvate conversion and repression of the tricarboxylic acid cycle. The direct transcriptional upregulation of metabolic genes is PI3K/Akt independent and occurs not only in cells with overactivated Notch but also in cells with endogenous levels of Notch signalling and in vivo. Even a short pulse of Notch activity is able to elicit long-lasting metabolic changes resembling the Warburg effect. Loss of Notch signalling in Drosophila wing discs as well as in human microvascular cells leads to downregulation of glycolytic genes. Notch-driven tissue overgrowth can be rescued by downregulation of genes for glucose metabolism. Notch activity is able to support growth of wing during nutrient-deprivation conditions, independent of the growth of the rest of the body. Notch is active in situations that involve metabolic reprogramming, and the direct regulation of metabolic genes may be a common mechanism that helps Notch to exert its effects in target tissues.

• Klíčová slova
• Notch targets, Warburg effect, glycolytic shift, metabolism, tissue growth,
• MeSH
• aktivace transkripce MeSH
• biologické modely MeSH
• buněčné linie MeSH
• citrátový cyklus genetika   MeSH
• energetický metabolismus genetika   MeSH
• exprese genu MeSH
• glykolýza genetika   MeSH
• lidé MeSH
• promotorové oblasti (genetika) MeSH
• proteiny Drosophily genetika   metabolismus   MeSH
• receptory Notch genetika   metabolismus   MeSH
• regulace genové exprese * MeSH
• regulační oblasti nukleových kyselin MeSH
• reportérové geny MeSH
• represorové proteiny genetika   metabolismus   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteiny Drosophily MeSH
• receptory Notch MeSH
• represorové proteiny MeSH
• Su(H) protein, Drosophila MeSH Prohlížeč

• Klíčová slova
• CITRATES/metabolism *,
• MeSH
• biochemické jevy * MeSH
• citrátový cyklus * MeSH
• citráty metabolismus   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• citráty MeSH

Trypanosoma brucei, a protist responsible for human African trypanosomiasis (sleeping sickness), is transmitted by the tsetse fly where the procyclic forms of the parasite develop in the proline-rich (1-2 mM) and glucose-depleted digestive tract. Proline is essential for the midgut colonization of the parasite in the insect vector, however other carbon sources could be available and used to feed its central metabolism. Here we show that procyclic trypanosomes can consume and metabolize metabolic intermediates, including those excreted from glucose catabolism (succinate, alanine and pyruvate), with the exception of acetate, which is the ultimate end-product excreted by the parasite. Among the tested metabolites, tricarboxylic acid (TCA) cycle intermediates (succinate, malate and α-ketoglutarate) stimulated growth of the parasite in the presence of 2 mM proline. The pathways used for their metabolism were mapped by proton-NMR metabolic profiling and phenotypic analyses of thirteen RNAi and/or null mutants affecting central carbon metabolism. We showed that (i) malate is converted to succinate by both the reducing and oxidative branches of the TCA cycle, which demonstrates that procyclic trypanosomes can use the full TCA cycle, (ii) the enormous rate of α-ketoglutarate consumption (15-times higher than glucose) is possible thanks to the balanced production and consumption of NADH at the substrate level and (iii) α-ketoglutarate is toxic for trypanosomes if not appropriately metabolized as observed for an α-ketoglutarate dehydrogenase null mutant. In addition, epimastigotes produced from procyclics upon overexpression of RBP6 showed a growth defect in the presence of 2 mM proline, which is rescued by α-ketoglutarate, suggesting that physiological amounts of proline are not sufficient per se for the development of trypanosomes in the fly. In conclusion, these data show that trypanosomes can metabolize multiple metabolites, in addition to proline, which allows them to confront challenging environments in the fly.

• MeSH
• citrátový cyklus účinky léků   MeSH
• glukosa metabolismus   MeSH
• hmyz - vektory parazitologie   MeSH
• moucha tse-tse účinky léků   parazitologie   MeSH
• oxidace-redukce účinky léků   MeSH
• prolin metabolismus   farmakologie   MeSH
• RNA interference fyziologie   MeSH
• Trypanosoma brucei brucei účinky léků   metabolismus   MeSH
• Trypanosoma účinky léků   metabolismus   MeSH
• trypanozomóza africká farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glukosa MeSH
• prolin MeSH

The authors studied the effect of calcium-free saline-glucose medium on labelled amino acid and [14C]CO2 synthesis from U-[14C]-glucose and 1-[14C]-acetate in rat brain cortex slices. Respiration was stimulated parallel with increased synthesis of labelled amino acids and of [14C]CO2 from glucose to [to 150 % and 170 % respectively]. Specific glutamate, aspartate and neutral amino acid activity rose, GABA and glutamine were unaffected. Amino acid synthesis from 1-[14C]-acetate was inhibited [58%], while [14C]CO2 release was unchanged. This indicates that oxygen consumption via the tricarboxylase cycle associated with the small glutamate pool [and probably localized in the glia cells] did not alter in calcium-free medium, although conversion to amino acids was impaired.

• MeSH
• acetáty metabolismus   MeSH
• aminokyseliny metabolismus   MeSH
• citrátový cyklus účinky léků   MeSH
• glukosa metabolismus   MeSH
• glutamáty metabolismus   MeSH
• glutamin metabolismus   MeSH
• krysa rodu Rattus MeSH
• mozková kůra metabolismus   MeSH
• oxid uhličitý metabolismus   MeSH
• spotřeba kyslíku účinky léků   MeSH
• techniky in vitro MeSH
• vápník farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetáty MeSH
• aminokyseliny MeSH
• glukosa MeSH
• glutamáty MeSH
• glutamin MeSH
• oxid uhličitý MeSH
• vápník MeSH

The authors compared, in rat brain cortex slices, the oxidation of labelled glucose and acetate and the conversion of these precursors into amino acids during incubation in control salt-glucose medium and in medium with 47 mM K+, with the aim of determining with which of the two determinable tricarboxylate cycles raised oxygen consumption is associated in the presence of excess K+. Under the experimental conditions it was found that from U-[14C]-glucose more than double the amount of [14C]-CO2 was formed and that the rate of [14C] incorportation into the amino acids was likewise roughly doubled. This is indicative of activation of processes in the tricarboxylate cycle associated with the large glutamate pool. Incorporation from 1-[14C]-acetate into the total amino acids was not affected. Specific activity in glutamate and asparate was more than doubled, while glutamine specific activity fell to less than half. [14C]-CO2 production fell to 65%. This shows that the tricarboxylate cycle associated with the small glutamate pool, which is probably localized in the glia cells, did not participate in raised oxygen consumption in the presence of excess K+.

• MeSH
• acetáty metabolismus   MeSH
• adenosintrifosfát metabolismus   MeSH
• aminokyseliny metabolismus   MeSH
• citrátový cyklus účinky léků   MeSH
• draslík farmakologie   MeSH
• GABA metabolismus   MeSH
• glukosa metabolismus   MeSH
• glutamáty metabolismus   MeSH
• glutamin metabolismus   MeSH
• krysa rodu Rattus MeSH
• kyselina aspartová metabolismus   MeSH
• mozková kůra metabolismus   MeSH
• oxid uhličitý metabolismus   MeSH
• spotřeba kyslíku účinky léků   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetáty MeSH
• adenosintrifosfát MeSH
• aminokyseliny MeSH
• draslík MeSH
• GABA MeSH
• glukosa MeSH
• glutamáty MeSH
• glutamin MeSH
• kyselina aspartová MeSH
• oxid uhličitý MeSH

• Klíčová slova
• AMINOBUTYRIC ACID *, CAROTID ARTERIES *, CEREBRAL CORTEX *, CHROMATOGRAPHY *, ELECTROENCEPHALOGRAPHY *, EXPERIMENTAL LAB STUDY *, ISCHEMIA *, KREBS CYCLE *, LACTATES *, PHYSIOLOGY *, POTASSIUM *, PYRUVATES *, RATS *, SOLUTIONS *, STRYCHNINE *,
• MeSH
• aminobutyráty * MeSH
• arteriae carotides * MeSH
• chromatografie * MeSH
• citrátový cyklus * MeSH
• deprese * MeSH
• draslík * MeSH
• elektroencefalografie * MeSH
• fyziologie * MeSH
• GABA * MeSH
• ischemie * MeSH
• krysa rodu Rattus MeSH
• laktáty * MeSH
• mozková kůra * MeSH
• pyruváty * MeSH
• roztoky * MeSH
• strychnin * MeSH
• výzkum * MeSH
• Check Tag
• krysa rodu Rattus MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminobutyráty * MeSH
• draslík * MeSH
• GABA * MeSH
• laktáty * MeSH
• pyruváty * MeSH
• roztoky * MeSH
• strychnin * MeSH