Influence of the metabolism of ethanol on the lactate/pyruvate ratio of rat-liver slices.
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ABSTRACT:
SUBMITTER: Forsander OA
PROVIDER: S-EPMC1264821 | biostudies-other | 1966 Jan
REPOSITORIES: biostudies-other
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Project description:ObjectivesTo assess the accuracy of blood lactate and lactate: pyruvate molar ratio (L:P) as a screen for mitochondrial, respiratory chain, or fatty acid oxidation disorders in children with pediatric acute liver failure (PALF); to determine whether serum lactate ≥ 2.5 mmol/L or L:P ≥ 25 correlated with biochemical variables of clinical severity; and to determine whether lactate or L:P is associated with clinical outcome at 21 days.Study designRetrospective review of demographic, clinical, laboratory, and outcome data for PALF study group participants who had lactate and pyruvate levels collected on the same day.ResultsOf 986 participants, 110 had lactate and pyruvate levels collected on the same day. Of the 110, the etiology of PALF was a mitochondrial disorder in 8 (7%), indeterminate in 65 (59%), and an alternative diagnosis in 37 (34%). Lactate, pyruvate, and L:P were similar among the 3 etiologic groups. There was no significant association between the initial lactate or L:P and biochemical variables of clinical severity or clinical outcome at 21 days.ConclusionsA serum lactate ≥ 2.5 mmol/L and/or elevated L:P was common in all causes of PALF, not limited to those with a mitochondrial etiology, and did not predict 21-day clinical outcome.Trial registrationClinicalTrials.gov: NCT00986648.
| S-EPMC5328928 | biostudies-literature
Project description:Menthofuran is a monoterpene present in mint plants that is oxidized by mammalian cytochrome P450 (CYP) to hepatotoxic metabolites. Evidence has been presented that p-cresol and other unusual oxidative products are metabolites of menthofuran in rats and that p-cresol may be responsible in part for the hepatotoxicity caused by menthofuran [ Madyastha, K. M. and Raj, C. P. (1992) Drug Metab. Dispos. 20, 295 - 301]. In the present study, several oxidative metabolites of menthofuran were characterized in rat and human liver microsomes and in rat liver slices exposed to cytotoxic concentrations of menthofuran. Metabolites that were identified were monohydroxylation products of the furanyl and cyclohexyl groups, mintlactones and hydroxymintlactones, a reactive γ-ketoenal, and a glutathione conjugate. A similar spectrum of metabolites was found in urine 24 h after the administration of hepatotoxic doses of menthofuran to rats. In no case was p-cresol (or any of the other reported unusual oxidative metabolites of menthofuran) detected above background concentrations that were well below concentrations of p-cresol that cause cytotoxicity in rat liver slices. Thus, the major metabolites responsible for the hepatotoxic effects of menthofuran appear to be a γ-ketoenal and/or epoxides formed by oxidation of the furan ring.
| S-EPMC2981629 | biostudies-literature
Project description:The influence of some aliphatic alcohols on oxygen uptake, carbon dioxide production, acid formation and lactate and pyruvate concentrations of rat liver slices was studied. At the concentrations used, none of the alcohols was found to influence oxygen uptake. Of the alcohols that are not oxidized by liver alcohol dehydrogenase, methanol increased carbon dioxide production, propan-2-ol decreased it and 2-methylpropan-2-ol was without influence. All the alcohols that are oxidized by the enzyme strongly decreased carbon dioxide production. The alcohols that are not oxidized had no marked effect on the lactate/pyruvate concentration ratio, whereas the other alcohols strongly increased the ratio. A highly significant correlation was found between the effects of the alcohol on pyruvate concentration and carbon dioxide production. It is assumed that the shift in the redox potential inhibits the function of the tricarboxylic acid cycle of the liver.
| S-EPMC1198278 | biostudies-other
Project description:1. Rates of gluconeogenesis in the perfused rat liver from propionate, l-lactate, pyruvate and the combination of propionate with either lactate or pyruvate were measured. Less than additive rates were obtained with either propionate plus lactate or propionate plus pyruvate. 2. The uptake of pyruvate plus lactate from the perfusion medium was decreased more seriously when propionate was present with lactate than with pyruvate. 3. The use of [2-(14)C]pyruvate in the presence of propionate showed that the decreased disappearance of pyruvate plus lactate did not result in their formation from propionate. 4. The addition of sodium butyrate to the perfusion medium caused an inhibition of gluconeogenesis from propionate and stimulated gluconeogenesis and uptake of pyruvate and lactate. 5. The observations are consistent with there being a sparing effect of propionate on lactate and pyruvate metabolism.
| S-EPMC1178695 | biostudies-other
Project description: Not available
| S-EPMC4206457 | biostudies-literature
Project description:Glycine decarboxylase (GLDC) gene is frequently upregulated in various types of cancer including lung, prostate and brain. It catabolizes glycine to yield 5,10-methylenetetrahydrofolate, an important substrate in one-carbon metabolism for nucleotide synthesis. In this study, we used exon splicing modulating steric hindrance antisense oligonucleotide (shAON) to suppress GLDC expression and investigated its effect on pyruvate metabolism via hyperpolarized carbon-13 magnetic resonance spectroscopy (MRS). The MRS technique allows us to study in vivo metabolic flux in tumor tissues with/without GLDC-shAON intervention. Here, we show that GLDC-shAON treatment is able to suppress lung cancer cell growth and tumorigenesis, both in vitro and in vivo. The carbon-13 MRS results indicated that the conversion of pyruvate into lactate in GLDC-shAON-treated tumor tissues was significantly reduced, when compared with the control groups. This observation corroborated with the reduced activity of lactate dehydrogenase and pyruvate dehydrogenase in GLDC-shAON-treated lung cancer cells and tumor tissues. Glycolysis stress test showed that extracellular acidification rate was significantly suppressed after GLDC-shAON treatment. Besides lung cancer, the antitumor effect of GLDC-shAON was also observed in brain, liver, cervical, and prostate cancer cell lines. Furthermore, it enhanced the treatment efficacy of cisplatin in lung cancer cells. Taken together, our findings illustrate that pyruvate metabolism decreases upon GLDC inhibition, thereby starving cancer cells from critical metabolic fuels.
| S-EPMC5992284 | biostudies-literature
Project description:In the present study we investigated whether isolated rat liver mitochondria can take up and metabolize D-lactate. We found the following: (1) externally added D-lactate causes oxygen uptake by mitochondria [P/O ratio (the ratio of mol of ATP synthesized to mol of oxygen atoms reduced to water during oxidative phosphorylation)=2] and membrane potential (Delta(psi)) generation in processes that are rotenone-insensitive, but inhibited by antimycin A and cyanide, and proton release from coupled mitochondria inhibited by alpha-cyanocinnamate, but not by phenylsuccinate; (2) the activity of the putative flavoprotein (D-lactate dehydrogenase) was detected in inside-out submitochondrial particles, but not in mitochondria and mitoplasts, as it is localized in the matrix phase of the mitochondrial inner membrane; (3) three novel separate translocators exist to mediate D-lactate traffic across the mitochondrial inner membrane: the D-lactate/H(+) symporter, which was investigated by measuring fluorimetrically the rate of endogenous flavin reduction, the D-lactate/oxoacid antiporter (which mediates both the D-lactate/pyruvate and D-lactate/oxaloacetate exchanges) and D-lactate/malate antiporter studied by monitoring photometrically the appearance of the D-lactate counteranions outside mitochondria. The D-lactate translocators, in the light of their different inhibition profiles separate from the monocarboxylate carrier, were found to differ from each other in the V(max) values and in the inhibition and pH profiles and were shown to regulate mitochondrial D-lactate metabolism in vitro. The D-lactate translocators and the D-lactate dehydrogenase could account for the removal of the toxic methylglyoxal from cytosol, as well as for D-lactate-dependent gluconeogenesis.
| S-EPMC1222695 | biostudies-other
Project description:In order to obtain a global view of energy metabolism pathways of the sulfate-reducer Desulfovibrio vulgaris Hildenborough and the proteins involved therein whole-genome microarrays were used to compare the transcriptional response of cells grown with hydrogen/sulfate, pyruvate/sulfate, lactate/thiosulfate, and pyruvate with limiting sulfate, relative to growth in standard lactate/sulfate condition. Growth with hydrogen/sulfate showed the largest number of differently expressed genes and the largest changes in expression levels. The most up-regulated energy metabolism genes were those coding for the periplasmic [NiFeSe] hydrogenase, followed by the Ech hydrogenase, and the most down-regulated were genes coding for the Coo hydrogenase. The results point to the involvement of formate cycling and the ethanol pathway during growth on hydrogen, whereas there is evidence for CO cycling during growth on lactate and pyruvate, but not on H2. Growth with thiosulfate showed the hallmarks of a reduced energy status of the cells with down regulation of the ATP synthase and the Qmo and Dsr complexes., whereas growth with pyruvate showed the smallest differences but an increased role for the Ech hydrogenase.that in this case functions in reverse from the case of growth with H2. The multiple periplasmic hydrogenases and formate dehydrogenases, do not display the same regulation pattern showing that their metabolic roles are not totally interchangeable. This result together with the observation that several genes coding for proteins that have not been biochemically characterised were considerably affected in this study, reveals a more complex energy metabolism than previously considered and provides guidance for further studies. Keywords: Growth protocol Desulfovibrio vulgaris from our laboratory culture collection was cultured at 37°C with pyruvate as the only substrate (without sulfate as the electron acceptor) to mid-log phase. Cultures were also cultivated similarly in Lactate-Sulfate medium to mid-log phase. Gene expression profiles of cultures grown under pyruvate fermentation were compared with those of the cultures grown via sulfate reduction. Total RNA was harvested from four replicate cultures for microarray analysis. RNA extraction, purification, and labeling were performed independently on each cell sample.Two samples of each total RNA preparation were labeled, one with Cy3-dUTP and another with Cy5-dUTP for microarray hybridization.
2008-05-31 | E-GEOD-8015 | biostudies-arrayexpress
Project description:Objective Although aerobic exercise tests on cycle ergometry have long been used for initial assessments of cases of suspected mitochondrial disease, the test parameters in patients with final diagnoses of other diseases via the widely used 15 W for 15 minutes exercise protocol have not been fully characterized. Methods We retrospectively reviewed all patients who underwent the test at our institution. We classified the patients with genetic diagnoses or those who met previously reported clinical criteria as having mitochondrial diseases and those with a final diagnosis of another disease as having other diseases. Results were available from 6 patients with mitochondrial disease and 15 with other diseases. Results During the test, elevated venous peak lactate above the upper normal limit of healthy controls at rest [19.2 mg/dL (2.13 mM)] was observed in 3 patients with mitochondrial diseases (50.0%) and 5 with other diseases (33.3%). In the group of patients with elevated venous peak lactate, a lactate-to-pyruvate ratio of >20 was observed in all 3 patients with mitochondrial disease but in only 1 of the 5 with other diseases. More than a 2-fold increase in venous lactate from baseline was observed in 4 patients with mitochondrial disease (66.7%) and 1 with another disease (6.7%). Conclusion Elevated venous peak lactate levels were observed in patients with final diagnoses of other diseases, even under a low 15-minute workload at 15 W. The lactate-to-pyruvate ratio and increase in lactate level from baseline may add diagnostic value to venous peak lactate levels alone.
| S-EPMC9334250 | biostudies-literature
Project description:1. The influence of ethanol on the metabolism of livers from fed and starved rats has been studied in liver-perfusion experiments. Results have been obtained on oxygen consumption and carbon dioxide production, on glucose release and uptake by the liver and on changes in the concentrations of lactate and pyruvate and of beta-hydroxybutyrate and acetoacetate in the perfusion medium. 2. Oxygen consumption and carbon dioxide production were lower in livers from starved rats than in livers from fed rats. Ethanol had no effect on the oxygen consumption of either type of liver. After the addition of ethanol to the perfusion medium carbon dioxide production ceased almost completely, the change being faster in livers from starved rats. 3. With livers from fed rats glucose was released from the liver into the perfusion medium. This release was slightly greater when ethanol was present. With livers from starved rats no release of glucose was observed, and when ethanol was added a marked uptake of glucose from the medium was found. A simultaneous release of glycolytic end products, lactate and pyruvate, into the medium occurred. 4. Acetate was the main metabolite accumulating in the perfusion medium when ethanol was oxidized. With livers from starved rats a slightly increased formation of ketone bodies was found when ethanol was present. 5. The lactate/pyruvate concentration ratio in the perfusion medium increased from 10 to 87 with livers from fed rats and from 20 to 171 with livers from starved rats when the livers were perfused with ethanol in the medium. The beta-hydroxybutyrate/acetoacetate concentration ratio increased from 0.8 to 7.6 with livers from fed rats and from 1.0 to 9.5 with livers from starved rats when ethanol was added to the medium. 6. The effects of ethanol are discussed and related to changes in the redox state of the liver that produce new conditions for some metabolic pathways.
| S-EPMC1206436 | biostudies-other