scholarly journals The effect of fumarate on respiration

The recent work of Szent-Gyorgyi and his co-workers (Gozsy and Szent-Gyorgyi, 1934; Annau et al .,1935) on the importance of fumarate in cellular respiration assigns a definite and fundamental function to the di-carboxylic four-carbon-atom acids and to the enzymes which activate them. Essentially their view is as follows: the reversible system, fumarate-oxalacetate, functions catalytically in transporting activated hydrogen from the metabolite dehydrogenation systems to the cytochrome (Warburg-Keilin) system through the medium of an intermediary substance. The oxalacetate formed takes up hydrogen, going either to fumarate, or to succinate by “ over-reduction ”. The succinate thus formed is converted to fumarate by means of succinodehydrogenase, and the catalytic cycle is completed. Malonate is known to inhibit succinodehydrogenase (Quastel and Wooldridge, 1928), and malonate also inhibits respiration. SzentGyorgyi et al . explain this inhibition by the fact that the succinate normally formed is prevented by malonate from being oxidized to fumarate, and respiration fails owing to a lack of fumarate. They further attribute the decrease in respiration of muscle tissue in vitro to a loss of fumarate through diffusion. If, however, this loss is compensated for by the addition of fresh fumarate, respiration proceeds normally. The addition of fumarate therefore “ preserves ” the normal respiration of the tissue.

Author(s):  
Selva Bilge ◽  
Emre Ergene ◽  
Ebru Talak ◽  
Seyda Gokyer ◽  
Yusuf Osman Donar ◽  
...  

AbstractSkeletal muscle is an electrically and mechanically active tissue that contains highly oriented, densely packed myofibrils. The tissue has self-regeneration capacity upon injury, which is limited in the cases of volumetric muscle loss. Several regenerative therapies have been developed in order to enhance this capacity, as well as to structurally and mechanically support the defect site during regeneration. Among them, biomimetic approaches that recapitulate the native microenvironment of the tissue in terms of parallel-aligned structure and biophysical signals were shown to be effective. In this study, we have developed 3D printed aligned and electrically active scaffolds in which the electrical conductivity was provided by carbonaceous material (CM) derived from algae-based biomass. The synthesis of this conductive and functional CM consisted of eco-friendly synthesis procedure such as pre-carbonization and multi-walled carbon nanotube (MWCNT) catalysis. CM obtained from biomass via hydrothermal carbonization (CM-03) and its ash form (CM-03K) were doped within poly(ɛ-caprolactone) (PCL) matrix and 3D printed to form scaffolds with aligned fibers for structural biomimicry. Scaffolds were seeded with C2C12 mouse myoblasts and subjected to electrical stimulation during the in vitro culture. Enhanced myotube formation was observed in electroactive groups compared to their non-conductive counterparts and it was observed that myotube formation and myotube maturity were significantly increased for CM-03 group after electrical stimulation. The results have therefore showed that the CM obtained from macroalgae biomass is a promising novel source for the production of the electrically conductive scaffolds for skeletal muscle tissue engineering.


1924 ◽  
Vol 62 (2) ◽  
pp. 453-469
Author(s):  
Christen Lundsgaard ◽  
Svend Aage Holbøll
Keyword(s):  

1929 ◽  
Vol 50 (3) ◽  
pp. 315-326 ◽  
Author(s):  
F. Duran-Reynals ◽  
James B. Murphy

Ground muscle from susceptible chickens fixes in vitro in a proportion of instances the agent of the filterable Chicken Tumor I, and in a lesser degree inactivates it, whereas the muscle from resistant animals such as rabbit and pigeon, is without effect. It is shown that the power of fixation of the chicken muscle is far greater than its inactivating properties. Brain and liver from chicken, rabbit and pigeon seem devoid of any action on the agent. The desiccated chicken muscle tissue shares the properties of the fresh organ; and the process of desiccation does not release the agent from the inactive or slightly active mixture of fresh muscle and filtrate.


Author(s):  
Lyudmyla Buyun ◽  
Oleksandr Gyrenko ◽  
Maryna Opryshko ◽  
Lyudmyla Kovalska ◽  
Halyna Tkachenko ◽  
...  

This research aimed to evaluate the in vitro effect of buffer extract obtained from leaves and pseudobulbs (modified shoots) of Dendrobium parishii Rchb. f. on the 2-thiobarbituric acid reactive substances (TBARS) as lipid peroxidation biomarker, aldehydic and ketonic derivatives of oxidatively modified proteins, and total antioxidant capacity (TAC) in the muscle tissue of the rainbow trout (Oncorhynchus mykiss Walbaum). The shoots (pseudobulbs) with leaves of Dendrobium parishii cultivated under glasshouse conditions were sampled at M.M. Gryshko National Botanic Garden (NBG) (Kyiv, Ukraine). Since 1999, the whole collection of tropical and subtropical plants (including orchids) has had the status of a National Heritage Collection of Ukraine and is supported through State funding. Besides, NBG’s collection of tropical orchids was registered at the Administrative Organ of CITES in Ukraine (Ministry of Environment Protection, registration No. 6939/19/1-10 of 23 June 2004). The collected pseudobulbs and leaves were brought into the laboratory for biochemical studies. Freshly collected leaves were washed, weighed, crushed, and homogenized in 0.1M phosphate buffer (pH 7.4) (in proportion 1:19, w/w) at room temperature. The extract was then filtered and investigated for its antioxidant capacity. The extract was stored at -20°C until use. The increase in TBARS level in the muscle tissue exposed to extracts derived from leaves and pseudobulbs of D. parishii was insignificant. The level of ketonic derivatives of oxidatively modified proteins was non-significantly decreased both for leaf and pseudobulb extracts compared to the untreated samples. The extracts obtained from leaves and pseudobulbs of D. parishii significantly increased the TAC level in muscle tissue due to inhibited the Fe2+/ascorbate-induced oxidation of Tween 80. Overall, these findings demonstrate that aqueous extracts of vegetative organs of Dendrobium parishii can enhance the total antioxidant capacity in the muscle tissue of the rainbow trout. Moreover, this antioxidant effect was more intensive for pseudobulb extracts.


2009 ◽  
Vol 296 (4) ◽  
pp. L657-L665 ◽  
Author(s):  
Mohammad Abolhassani ◽  
Adeline Guais ◽  
Philippe Chaumet-Riffaud ◽  
Annie J. Sasco ◽  
Laurent Schwartz

The aim of this study was to assess whether one of the most common poisons of cellular respiration, i.e., carbon dioxide, is proinflammatory. CO2 is naturally present in the atmosphere at the level of 0.038% and involved in numerous cellular biochemical reactions. We analyzed in vitro the inflammation response induced by exposure to CO2 for 48 h (0–20% with a constant O2 concentration of 21%). In vivo mice were submitted to increasing concentrations of CO2 (0, 5, 10, and 15% with a constant O2 concentration of 21%) for 1 h. The exposure to concentrations above 5% of CO2 resulted in the increased transcription (RNase protection assay) and secretion (ELISA) of proinflammatory cytokines [macrophage inflammatory protein-1α (MIP-1α), MIP-1β, MIP-2, IL-8, IL-6, monocyte chemoattractant protein-1, and regulated upon activation, normal T cell expressed, and, presumably, secreted (RANTES)] by epithelial cell lines HT-29 or A549 and primary pulmonary cells retrieved from the exposed mice. Lung inflammation was also demonstrated in vivo by mucin 5AC-enhanced production and airway hyperreactivity induction. This response was mostly mediated by the nuclear translocation of p65 NF-κB, itself a consequence of protein phosphatase 2A (PP2A) activation. Short inhibiting RNAs (siRNAs) targeted toward PP2Ac reversed the effect of carbon dioxide, i.e., disrupted the NF-κB activation and the proinflammatory cytokine secretion. In conclusion, this study strongly suggests that exposure to carbon dioxide may be more toxic than previously thought. This may be relevant for carcinogenic effects of combustion products.


2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S30-S31
Author(s):  
Gabriel Suarez ◽  
Bo Liu ◽  
Jeremy Herzog ◽  
Ryan Sartor

Abstract Sulfur metabolism is emerging as a signature of IBD gut microbiota. Overrepresentation of sulfur-reducing bacteria (SRB) in IBD results in SRB-derived epithelial toxic H2S production that can overwhelm the body’s detoxification capacity, leading to impaired cellular respiration by inhibiting oxygen binding to mitochondrial cytochrome-c-oxidase. Butyrate potently inhibits SRBs and H2S, yet IBD patients have reduced short chain fatty acid (SCFA) production. More critically, H2S blocks butyrate oxidation, the primary energy source of colonocytes; butyrate oxidation deficiency is a defining characteristic of IBD. Since cysteine is the preferred substrate for H2S production by SRBs, a cysteine-rich environment provided by either a high protein diet or local intestinal mucus degradation promotes ideal conditions for SRB establishment and proliferation. SRBs can catabolize other sulfur-containing compounds critical for immune homeostasis and cellular health, such as taurine-conjugated bile acids and the “master antioxidant” glutathione, leading to further toxic H2S production. However, the molecular underpinnings of sulfur metabolism by specific bacterial genera is understudied in IBD. Results: Using a combination of in-vivo and in-vitro screening to detect the relative induction of interleukin 10 (IL-10) and interferon g (IFNg) by 19 resident bacterial strains isolated from a healthy human donor, we identified 4 bacterial strains that induce a low IL-10/IFNg ratio. These 4 strains (low group), but not 3 bacterial strains that induce a high IL-10/IFNg ratio, induce colitis in selectively colonized gnotobiotic Il10-/- mice (Fig.1A). Two of these 4 disease-inducing strains, Clostridium perfringens (A12) and Clostridium bolteae (B6), produce high concentrations of H2S in monoassociated mice (Fig.1B). In-vitro H2S production by these strains is dependent on cysteine (Fig.1C). C. perfringens and C. bolteae each induce colitis in monoassociated Il10-/- mice (Fig.1D). We are dissecting the sulfur metabolic pathways in C. perfringens and C. bolteae and their contribution to inflammatory processes by interrupting key genes predicted to contribute to H2S production, cysteine catabolism and bile acid metabolism. We will use these mutants in both in-vitro and in-vivo Il10 -/- gnotobiotic mice models to characterize their metabolic and inflammatory profiles. We have created several mutants using Targetron gene editing, including the dissimilatory sulfate reductase (Δdsr), a putative sulfonate membrane transporter (ΔssuA), anaerobic sulfite reductase (ΔasrA) and bile salt hydrolase (Δbsh). Conclusions: H2S producing bacterial strains can induce experimental colitis. Our planned mechanistic studies will determine the metabolic routes for H2S production by specific aggressive bacteria to guide novel therapeutic or dietary interventions to improve IBD prognosis.


Parasitology ◽  
1997 ◽  
Vol 114 (7) ◽  
pp. 91-99 ◽  
Author(s):  
J. A. URBINA

Inhibitors of sterol and phospholipid biosynthesis in kinetoplastid parasites such as Trypanosoma cruzi, the causative agent of Chagas' disease, and different species of Leishmania have potent and selective activity as chemotherapeutic agents in vitro and in vivo. Recent work with the sterol C14α-demethylase inhibitor D0870, a bis triazole derivative, showed that this compound is capable of inducing radical parasitological cure in murine models of both acute and chronic Chagas' disease. Other inhibitors of this type, such as SCH 56592, have also shown curative, rather than suppressive, activity against T. cruzi in these models. Leishmania species have different susceptibilities to sterol biosynthesis inhibitors, both in vitro and in vivo. Leishmania braziliensis promastigotes, naturally resistant to C14α-demethylase inhibitors such as ketoconazole and D0870, were susceptible to these drugs when used in combination with the squalene epoxidase inhibitor terbinafine. Inhibitors of Δ24(25) sterol methyl transferase have been shown to act as potent antiproliferative agents against Trypanosoma cruzi, both in vitro and in vivo. New inhibitors of this type which show enhanced activity and novel mechanisms of action have been synthesized. Recent work has also demonstrated that this type of enzyme inhibitors can block sterol biosynthesis and cell proliferation in Pneumocystis carinii, a fungal pathogen which had previously been found resistant to other sterol biosynthesis inhibitors. Ajoene, an antiplatelet compound derived from garlic, was shown to have potent antiproliferative activity against epimastigotes and amastigotes of Trypanosoma cruzi in vitro; this activity was associated with a significant alteration of the phospholipid composition of the cells with no significant effects on the sterol content. In addition, alkyllsophospholipids such as ilmofosine, miltefosine and edelfosine have been shown to block the proliferation of T. cruzi and Leishmania and alter both the phospholipid and sterol composition. These results indicate the potential of lipid biosynthesis inhibitors as useful therapeutic agents in the treatment of leishmaniasis and Chagas' disease.


2019 ◽  
Vol 12 (3) ◽  
pp. 110 ◽  
Author(s):  
Yuto Amano ◽  
Hiroshi Honda ◽  
Yuko Nukada ◽  
Naohiro Ikeda ◽  
Masayuki Yamane ◽  
...  

Although coffee components have gained interest for use as pharmaceuticals, little is known about their safety pharmacological effects. Hence, we aimed to evaluate the safety pharmacological effects of a chlorogenic acid (CGA)-related compound contained in coffee, 5-O-caffeoylquinic acid (5-CQA), and its metabolites, 5-O-feruloylquinic acid (5-FQA), caffeic acid (CA), and ferulic acid (FA). Langendorff perfused heart assay, electrophysiological assay of acute rat hippocampal slices, and in vitro Magnus assay of gastrointestinal tracts were conducted at 1–100 µM. Moreover, in vitro profiling assays against 38 major targets were conducted. In the Langendorff assay, no significant adverse effects were observed. In the electrophysiological assay, although epileptiform discharge rates were increased at 10 µM CA with 4-aminopyridine, and area under the curve (AUC) and number of population spike were increased at 10 µM FA with bicuculline, dose dependency was not confirmed, and no significant changes were observed at 1 µM and by CGAs alone. In the Magnus assay, a slight increase in contraction activity was observed at >1 µM FA in the stomach fundi and 100 µM 5-CQA in the ileum, suggesting enterokinesis promotion. No significant interactions were observed in the in vitro profiling assays. Therefore, CGAs could have a fundamental function as safe pharmaceuticals.


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