scholarly journals Glyoxylate detoxification is an essential function of malate synthase required for carbon assimilation inMycobacterium tuberculosis

2017 ◽  
Vol 114 (11) ◽  
pp. E2225-E2232 ◽  
Author(s):  
Susan Puckett ◽  
Carolina Trujillo ◽  
Zhe Wang ◽  
Hyungjin Eoh ◽  
Thomas R. Ioerger ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Isocitrate Lyase ◽  
Carbon Assimilation ◽  
Malate Synthase ◽  
Glyoxylate Shunt ◽  
Growth And Survival ◽  
Physiologic Function ◽  
Chain Fatty Acids

The glyoxylate shunt is a metabolic pathway of bacteria, fungi, and plants used to assimilate even-chain fatty acids (FAs) and has been implicated in persistence ofMycobacterium tuberculosis(Mtb). Recent work, however, showed that the first enzyme of the glyoxylate shunt, isocitrate lyase (ICL), may mediate survival ofMtbduring the acute and chronic phases of infection in mice through physiologic functions apart from fatty acid metabolism. Here, we report that malate synthase (MS), the second enzyme of the glyoxylate shunt, is essential for in vitro growth and survival ofMtbon even-chain fatty acids, in part, for a previously unrecognized activity: mitigating the toxicity of glyoxylate excess arising from metabolism of even-chain fatty acids. Metabolomic profiling revealed that MS-deficientMtbcultured on fatty acids accumulated high levels of the ICL aldehyde endproduct, glyoxylate, and increased levels of acetyl phosphate, acetoacetyl coenzyme A (acetoacetyl-CoA), butyryl CoA, acetoacetate, and β-hydroxybutyrate. These changes were indicative of a glyoxylate-induced state of oxaloacetate deficiency, acetate overload, and ketoacidosis. Reduction of intrabacterial glyoxylate levels using a chemical inhibitor of ICL restored growth of MS-deficientMtb, despite inhibiting entry of carbon into the glyoxylate shunt. In vivo depletion of MS resulted in sterilization ofMtbin both the acute and chronic phases of mouse infection. This work thus identifies glyoxylate detoxification as an essential physiologic function ofMtbmalate synthase and advances its validation as a target for drug development.

Short-Chain Fatty Acids Prevent Diabetic Nephropathy In Vivo and In Vitro

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 92-OR ◽  
Author(s):  
WEI HUANG ◽  
YONG XU ◽  
YOUHUA XU ◽  
LUPING ZHOU ◽  
CHENLIN GAO
Keyword(s):  
Fatty Acids ◽  
Diabetic Nephropathy ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Chain Fatty Acids

scholarly journals 2-Aminopyridine Analogs Inhibit Both Enzymes of the Glyoxylate Shunt in Pseudomonas aeruginosa

2020 ◽  
Vol 21 (7) ◽  
pp. 2490
Author(s):  
Alyssa C. McVey ◽  
Sean Bartlett ◽  
Mahmud Kajbaf ◽  
Annalisa Pellacani ◽  
Viviana Gatta ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Isocitrate Lyase ◽  
Opportunistic Pathogen ◽  
Malate Synthase ◽  
Cell Permeability ◽  
Titration Calorimetry ◽  
Glyoxylate Shunt ◽  
Nutrient Sources ◽  
Hospital Acquired

Pseudomonas aeruginosa is an opportunistic pathogen responsible for many hospital-acquired infections. P. aeruginosa can thrive in diverse infection scenarios by rewiring its central metabolism. An example of this is the production of biomass from C2 nutrient sources such as acetate via the glyoxylate shunt when glucose is not available. The glyoxylate shunt is comprised of two enzymes, isocitrate lyase (ICL) and malate synthase G (MS), and flux through the shunt is essential for the survival of the organism in mammalian systems. In this study, we characterized the mode of action and cytotoxicity of structural analogs of 2-aminopyridines, which have been identified by earlier work as being inhibitory to both shunt enzymes. Two of these analogs were able to inhibit ICL and MS in vitro and prevented growth of P. aeruginosa on acetate (indicating cell permeability). Moreover, the compounds exerted negligible cytotoxicity against three human cell lines and showed promising in vitro drug metabolism and safety profiles. Isothermal titration calorimetry was used to confirm binding of one of the analogs to ICL and MS, and the mode of enzyme inhibition was determined. Our data suggest that these 2-aminopyridine analogs have potential as anti-pseudomonal agents.

scholarly journals Long chain fatty acids: in vitro cholecystokinin production and in vivo energy intake and body composition alteration

2011 ◽  
Vol 70 (OCE3) ◽  
Author(s):  
C. J. Harden ◽  
A. N. Jones ◽  
T. Maya-Jimenez ◽  
M. E. Barker ◽  
N. J. Hepburn ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Body Composition ◽  
Energy Intake ◽  
Long Chain Fatty Acids ◽  
Long Chain ◽  
Chain Fatty Acids

The Athlete and Gut Microbiome: Short-chain Fatty Acids as Potential Ergogenic Aids for Exercise and Training

2021 ◽  
Author(s):  
Tindaro Bongiovanni ◽  
Marilyn Ong Li Yin ◽  
Liam Heaney
Keyword(s):  
Fatty Acids ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Future Research ◽  
Immune Functions ◽  
Additional Energy ◽  
Chain Fatty Acids

AbstractShort-chain fatty acids (SCFAs) are metabolites produced in the gut via microbial fermentation of dietary fibers referred to as microbiota-accessible carbohydrates (MACs). Acetate, propionate, and butyrate have been observed to regulate host dietary nutrient metabolism, energy balance, and local and systemic immune functions. In vitro and in vivo experiments have shown links between the presence of bacteria-derived SCFAs and host health through the blunting of inflammatory processes, as well as purported protection from the development of illness associated with respiratory infections. This bank of evidence suggests that SCFAs could be beneficial to enhance the athlete’s immunity, as well as act to improve exercise recovery via anti-inflammatory activity and to provide additional energy substrates for exercise performance. However, the mechanistic basis and applied evidence for these relationships in humans have yet to be fully established. In this narrative review, we explore the existing knowledge of SCFA synthesis and the functional importance of the gut microbiome composition to induce SCFA production. Further, changes in gut microbiota associated with exercise and various dietary MACs are described. Finally, we provide suggestions for future research and practical applications, including how these metabolites could be manipulated through dietary fiber intake to optimize immunity and energy metabolism.

scholarly journals Studies on lipid digestion in the preruminant calf

1978 ◽  
Vol 40 (1) ◽  
pp. 125-131 ◽  
Author(s):  
J. D. Edwards-Webb ◽  
S. Y. Thompson
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acids ◽  
Butyric Acid ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Esterified Fatty Acids ◽  
Chain Fatty Acids

1. The lipolysis of cow's milk fat by salivary lipase (EC 3.1.1.3) in the preruminant calf has been studied in vitro by a simulated abomasal digestion, and also in vivo by examining the abomasal effluent collected over 12 h after giving whole milk to a calf.2. In the in vitro experiment the liquid drained from the clot contained a higher proportion of short-chain fatty acids than the abomasal effluent in the in vivo experiment. This was considered to indicate the absorption of short-chain free fatty acids from within the abomasum.3. Preferential release of short-chain fatty acids both in vitro and in vivo was observed.4. The outflow of butyric acid from the abomasum of the calf was initially rapid, but had levelled off at approximately 6 h, whereas the outflow of a typical long-chain fatty acid (palmitic) was fairly constant over the 12 h.Butyric acid predominated in the free fatty acids of abomasal effluent 0.5 h after feeding (668 mmol/mol total free fatty acids) but had become a minor component by 12 h (15 mmol/mol total free fatty acids).5. The mean amounts of free and esterified fatty acids (mmol/mol fatty acid ingested) present in the abomasal effluent from the 12 h collection period were: triglyceride 465, diglyceride 215, monoglyceride 68, free fatty acid 252. These values showed that only one-third of esterified fatty acids ingested are lipolysed to absorbable products by salivary lipase.

scholarly journals Production, Structural Characterization, and In Vitro Assessment of the Prebiotic Potential of Butyl-Fructooligosaccharides

2020 ◽  
Vol 21 (2) ◽  
pp. 445 ◽  
Author(s):  
Sini Kang ◽  
Hyun Ju You ◽  
Yeong-Geun Lee ◽  
Yunju Jeong ◽  
Tony V. Johnston ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Negative Control ◽  
Short Chain ◽  
Control Group ◽  
Metabolic Genes ◽  
Chain Fatty Acids

Short-chain fatty acids (SCFAs), especially butyrate, produced in mammalian intestinal tracts via fermentation of dietary fiber, are known biofunctional compounds in humans. However, the variability of fermentable fiber consumed on a daily basis and the diversity of gut microbiota within individuals often limits the production of short-chain fatty acids in the human gut. In this study, we attempted to enhance the butyrate levels in human fecal samples by utilizing butyl-fructooligosaccharides (B-FOS) as a novel prebiotic substance. Two major types of B-FOS (GF3-1B and GF3-2B), composed of short-chain fructooligosaccharides (FOS) bound to one or two butyric groups by ester bonds, were synthesized. Qualitative analysis of these B-FOS using Fourier transform infrared (FT-IR) spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), nuclear magnetic resonance (NMR) and low-resolution fast-atom bombardment mass spectra (LR-FAB-MS), showed that the chemical structure of GF3-1B and GF3-2B were [O-(1-buty-β-D-fru-(2→1)-O-β-D-fru-(2→1)-O-β-D-fru-O-α-D-glu] and [O-(1-buty)-β-D-fru-(2→1)-O-β-D-fru-(2→1)-O-(4-buty)-β-D-fru-O-α-D-glu], respectively. The ratio of these two compounds was approximately 5:3. To verify their biofunctionality as prebiotic oligosaccharides, proliferation and survival patterns of human fecal microbiota were examined in vitro via 16S rRNA metagenomics analysis compared to a positive FOS control and a negative control without a carbon source. B-FOS treatment showed different enrichment patterns on the fecal microbiota community during fermentation, and especially stimulated the growth of major butyrate producing bacterial consortia and modulated specific butyrate producing pathways with significantly enhanced butyrate levels. Furthermore, the relative abundance of Fusobacterium and ammonia production with related metabolic genes were greatly reduced with B-FOS and FOS treatment compared to the control group. These findings indicate that B-FOS differentially promotes butyrate production through the enhancement of butyrate-producing bacteria and their metabolic genes, and can be applied as a novel prebiotic compound in vivo.

scholarly journals Effect of Chestnut Tannins and Short Chain Fatty Acids as Anti-Microbials and as Feeding Supplements in Broilers Rearing and Meat Quality

Animals ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 659 ◽  
Author(s):  
Federica Mannelli ◽  
Sara Minieri ◽  
Giovanni Tosi ◽  
Giulia Secci ◽  
Matteo Daghio ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Meat Quality ◽  
Short Chain Fatty Acids ◽  
Control Group ◽  
Poultry Production ◽  
Vitro Assay ◽  
Promising Alternative ◽  
Chain Fatty Acids

Chestnut tannins (CT) and saturated short medium chain fatty acids (SMCFA) are valid alternatives to contrast the growth of pathogens in poultry rearing, representing a valid alternative to antibiotics. However, the effect of their blends has never been tested. Two blends of CT extract and Sn1-monoglycerides of SMCFA (SN1) were tested in vitro against the proliferation of Clostridium perfringens, Salmonella typhymurium, Escherichia coli, Campylobacter jejuni. The tested concentrations were: 3.0 g/kg of CT; 3.0 g/kg of SN1; 2.0 g/kg of CT and 1.0 g/kg of SN1; 1.0 g/kg of CT and 2.0 g/kg of SN1. Furthermore, their effect on broiler performances and meat quality was evaluated in vivo: one-hundred Ross 308 male birds were fed a basal diet with no supplement (control group) or supplemented with CT or SN1 or their blends at the same concentration used in the in vitro trial. The in vitro assay confirmed the effectiveness of the CT and SN1 mixtures in reducing the growth of the tested bacteria while the in vivo trial showed that broiler performances, animal welfare and meat quality were not negatively affected by the blends, which could be a promising alternative in replacing antibiotics in poultry production.

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