-
Neurogastroenterology and Motility Nov 2014Colonic microbiota digest resistant starches producing short chain fatty acids (SCFAs). The main SCFAs produced are acetate, propionate, and butyrate. Both excitatory...
BACKGROUND
Colonic microbiota digest resistant starches producing short chain fatty acids (SCFAs). The main SCFAs produced are acetate, propionate, and butyrate. Both excitatory and inhibitory effects of SCFAs on motility have been reported. We hypothesized that the effect of SCFAs on colonic motility varies with chain length and aimed to determine the effects of SCFAs on propagating and non-propagating contractions of guinea pig proximal and distal colon.
METHODS
In isolated proximal colonic segments, Krebs solution alone or containing 10-100 mM acetate, propionate, or butyrate was injected into the lumen, motility was videorecorded over 10 min, and spatiotemporal maps created. In distal colon, the lumen was perfused with the same solutions of SCFAs at 0.1 mL/min, the movement of artificial fecal pellets videorecorded, and velocity of propulsion calculated.
KEY RESULTS
In proximal colon, butyrate increased the frequency of full-length propagations, decreased short propagations, and had a biphasic effect on non-propagating contractions. Propionate blocked full and short propagations and had a biphasic effect on non-propagating contractions. Acetate decreased short and total propagations. In distal colon, butyrate increased and propionate decreased velocity of propulsion.
CONCLUSIONS & INFERENCES
The data suggest that luminal SCFAs have differing effects on proximal and distal colonic motility depending on chain length. Thus, the net effect of SCFAs on colonic motility would depend on the balance of SCFAs produced by microbial digestion of resistant starches.
Topics: Animals; Butyrates; Colon; Female; Gastrointestinal Motility; Guinea Pigs; Male; Organ Culture Techniques; Propionates
PubMed: 25223619
DOI: 10.1111/nmo.12425 -
Journal of Dairy Science May 2024Although postruminal glucose infusion into dairy cows has increased milk protein yield in some past experiments, the same trend has not been observed in others. A... (Meta-Analysis)
Meta-Analysis
Although postruminal glucose infusion into dairy cows has increased milk protein yield in some past experiments, the same trend has not been observed in others. A meta-regression of 64 sets of observations from 29 previously published glucose and propionate infusion studies in dairy cattle, treating study and experiment (study) as random effects, was performed to establish the general effects of glucose equivalent (GlcE) infusion rate on milk true protein (MTP) yield and content, if any, and to identify independent, fixed-effect variables that accounted for the changes in MTP yield and content that were observed. Candidate explanatory variables included rate and site of infusion, diet composition and intake, body weight and lactation stage of the cows, and the change in nutrient intake between GlcE and control treatments. Across all studies, according to a model containing only the random effects of study and experiment, GlcE infusion at an average of 954 g/d increased MTP yield by 26 g/d, on average, whereas mean MTP content was not affected. Backward stepwise elimination of potential explanatory variables from a full mixed model produced a final, reduced model for MTP yield that retained a positive, second-order quadratic effect of infusion rate of GlcE and a positive, linear effect of the change in crude protein intake (CPI) between GlcE treatment and control. This change in CPI due to GlcE infusion ranged from -0.546 to 0.173 kg/d in the dataset. The model fit indicated that when CPI was allowed to drop during GlcE infusion, the effect of GlcE on MTP yield was smaller than when CPI was maintained or increased, in a manifestation of the classic protein:energy interaction. The final reduced model for MTP content contained the same explanatory variables as for MTP yield, plus a negative effect of intravenous compared with gastrointestinal infusion. Overall, the meta-analysis revealed that both MTP yield, and content were positively related to GlcE infusion rate and to the change in CPI between glucose treatment and control.
Topics: Female; Cattle; Animals; Glucose; Propionates; Milk Proteins; Diet; Lactation
PubMed: 37806622
DOI: 10.3168/jds.2023-23644 -
American Journal of Physiology.... Oct 2017Propionate, 3-hydroxypropionate (3HP), methylcitrate, related compounds, and ammonium accumulate in body fluids of patients with disorders of propionyl-CoA metabolism,...
Propionate, 3-hydroxypropionate (3HP), methylcitrate, related compounds, and ammonium accumulate in body fluids of patients with disorders of propionyl-CoA metabolism, such as propionic acidemia. Although liver transplantation alleviates hyperammonemia, high concentrations of propionate, 3HP, and methylcitrate persist in body fluids. We hypothesized that conserved metabolic perturbations occurring in transplanted patients result from the simultaneous presence of propionate and 3HP in body fluids. We investigated the inter-relations of propionate and 3HP metabolism in perfused livers from normal rats using metabolomic and stable isotopic technologies. In the presence of propionate, 3HP, or both, we observed the following metabolic perturbations. First, the citric acid cycle (CAC) is overloaded but does not provide sufficient reducing equivalents to the respiratory chain to maintain the homeostasis of adenine nucleotides. Second, there is major CoA trapping in the propionyl-CoA pathway and a tripling of liver total CoA within 1 h. Third, liver proteolysis is stimulated. Fourth, propionate inhibits the conversion of 3HP to acetyl-CoA and its oxidation in the CAC. Fifth, some propionate and some 3HP are converted to nephrotoxic maleate by different processes. Our data have implications for the clinical management of propionic acidemia. They also emphasize the perturbations of the liver intermediary metabolism induced by supraphysiological, i.e., millimolar, concentrations of labeled propionate used to trace the intermediary metabolism, in particular, inhibition of CAC flux and major decreases in the [ATP]/[ADP] and [ATP]/[AMP] ratios.
Topics: Acyl Coenzyme A; Ammonium Compounds; Animals; Carbon Isotopes; Citrates; Citric Acid Cycle; Lactic Acid; Liver; Liver Transplantation; Male; Oxidation-Reduction; Propionates; Propionic Acidemia; Proteolysis; Rats; Rats, Sprague-Dawley
PubMed: 28634175
DOI: 10.1152/ajpendo.00105.2017 -
Cardiovascular Drugs and Therapy Dec 2009During reperfusion, following myocardial ischemia, uncompensated loss of citric acid cycle (CAC) intermediates may impair CAC flux and energy transduction. Propionate...
PURPOSE
During reperfusion, following myocardial ischemia, uncompensated loss of citric acid cycle (CAC) intermediates may impair CAC flux and energy transduction. Propionate has an anaplerotic effect when converted to the CAC intermediate succinyl-CoA, and may improve contractile recovery during reperfusion. Antioxidant therapy with N-acetylcysteine decreases reperfusion injury. To synergize the antioxidant effects of cysteine with the anaplerotic effects of propionate, we synthesized a novel bi-functional compound, N,S-dipropionyl cysteine ethyl ester (DPNCE) and tested its anaplerotic and anti-oxidative capacity in anesthetized pigs.
METHODS
Ischemia was induced by a 70% reduction in left anterior descending coronary artery flow for one hour, followed by 1 h of reperfusion. After 30 min of ischemia and throughout reperfusion animals were treated with saline or intravenous DPNCE (1.5 mg x kg(-1) x min(-1), n = 8/group). Arterial concentrations and myocardial propionate, cysteine, free fatty acids, glucose and lactate uptakes, cardiac mechanical functions, myocardial content of CAC intermediates and oxidative stress were assessed.
RESULTS
Ischemia resulted in reduction in myocardial tissue concentration of CAC intermediates. DPNCE treatment elevated arterial propionate and cysteine concentrations and myocardial propionate uptake, and increased myocardial concentrations of citrate, succinate, fumarate, and malate compared to saline treated animals. DPNCE treatment did not affect blood pressure or myocardial contractile function, but increased arterial free fatty acid concentration and myocardial fatty acid uptake. Arterial cysteine concentration was elevated by DPNCE, but there was negligible myocardial cysteine uptake, and no change in markers of oxidative stress.
CONCLUSION
DPNCE elevated arterial cysteine and propionate, and increased myocardial concentration of CAC intermediates, but did not affect mechanical function or oxidative stress.
Topics: Animals; Antioxidants; Citric Acid Cycle; Cysteine; Dose-Response Relationship, Drug; Gas Chromatography-Mass Spectrometry; Myocardial Reperfusion Injury; Oxidative Stress; Propionates; Swine
PubMed: 19967553
DOI: 10.1007/s10557-009-6208-1 -
Journal of Animal Science Jul 2016A combination of yeast and chromium propionate (Y+Cr) was added to the diets of crossbred finishing steers ( = 504; 402 kg ± 5.76 initial BW) to evaluate impact on... (Randomized Controlled Trial)
Randomized Controlled Trial
A combination of yeast and chromium propionate (Y+Cr) was added to the diets of crossbred finishing steers ( = 504; 402 kg ± 5.76 initial BW) to evaluate impact on feedlot performance and carcass traits. We hypothesized supplementation of Y+Cr would increase growth of feedlot steers. Steers with initial plasma glucose concentrations ≤6.0 m were stratified by initial BW and randomly allocated, within strata, to receive 0 (control) or 3.3 g/d Y+Cr. Steers were further divided into heavy and light weight blocks with 6 pens/diet within each weight block. Cattle were housed in dirt-surfaced pens with 21 steers/pen and had ad libitum access to feed. Body weights were measured at 21-d intervals. Blood samples were collected on d 49 and 94 from a subset of steers (5/pen) for analyses of plasma glucose and lactate concentrations. At the end of the finishing phase, animals were weighed and transported 450 km to an abattoir in Holcomb, KS. Severity of liver abscesses and HCW were collected the day of harvest, and after 36 h of refrigeration, USDA yield and quality grades, LM area, and 12th rib subcutaneous fat thickness were determined. There were no treatment × time × weight block interactions ( > 0.05) and no treatment × block interaction for ADG, DMI, or final BW ( ≥ 0.06), but a treatment × block interaction ( = 0.03) was observed for G:F, in which control, light cattle had poorer efficiency compared with other groups. Treatment × weight group interactions were observed for overall yield grade and carcasses that graded yield grade 1 ( ≤ 0.04). Light steers supplemented with Y+Cr had decreased overall yield grade and increased percentage of carcasses grading yield grade 1 compared with their control counterparts, with no differences observed for heavy steers. Regardless of weight group, a greater percentage of carcasses from steers supplemented with Y+Cr graded yield grade 2 ( = 0.03) and fewer carcasses from steers supplemented Y+Cr graded yield grade 3 ( < 0.01) than control steers. No interactions or effects of treatment were detected for other carcass measurements ( ≥ 0.07). There were no treatment × weight group interactions or effects of treatment for plasma glucose or lactate concentrations on d 49 or 94 ( > 0.10). Overall, yeast in combination with chromium propionate may improve feed efficiency and decrease yield grade of light cattle but had no effect on remaining carcass traits and blood constituents.
Topics: Animal Feed; Animals; Body Composition; Cattle; Diet; Drug Therapy, Combination; Male; Propionates; Saccharomyces cerevisiae; Weight Gain; Yeast, Dried
PubMed: 27482687
DOI: 10.2527/jas.2016-0454 -
Biomolecules Jan 2023Monoderm bacteria accumulate heme via the coproporphyrin-dependent biosynthesis pathway. In the final step, in the presence of two molecules of HO, the propionate...
Monoderm bacteria accumulate heme via the coproporphyrin-dependent biosynthesis pathway. In the final step, in the presence of two molecules of HO, the propionate groups of coproheme at positions 2 and 4 are decarboxylated to form vinyl groups by coproheme decarboxylase (ChdC), in a stepwise process. Decarboxylation of propionate 2 produces an intermediate that rotates by 90° inside the protein pocket, bringing propionate 4 near the catalytic tyrosine, to allow the second decarboxylation step. The active site of ChdCs is stabilized by an extensive H-bond network involving water molecules, specific amino acid residues, and the propionate groups of the porphyrin. To evaluate the role of these H-bonds in the pocket stability and enzyme functionality, we characterized, via resonance Raman and electronic absorption spectroscopies, single and double mutants of the actinobacterial pathogen ChdC complexed with coproheme and heme . The selective elimination of the H-bond interactions between propionates 2, 4, 6, and 7 and the polar residues of the pocket allowed us to establish the role of each H-bond in the catalytic reaction and to follow the changes in the interactions from the substrate to the product.
Topics: Heme; Hydrogen Bonding; Propionates; Hydrogen Peroxide; Corynebacterium diphtheriae; Carboxy-Lyases
PubMed: 36830604
DOI: 10.3390/biom13020235 -
Nuclear Medicine and Biology Jan 2015Amino acid based radiotracers target tumor cells through increased uptake by membrane-associated amino acid transport (AAT) systems. In the present study, four...
System a amino acid transport-targeted brain and systemic tumor PET imaging agents 2-amino-3-[(18)F]fluoro-2-methylpropanoic acid and 3-[(18)F]fluoro-2-methyl-2-(methylamino)propanoic acid.
INTRODUCTION
Amino acid based radiotracers target tumor cells through increased uptake by membrane-associated amino acid transport (AAT) systems. In the present study, four structurally related non-natural (18)F-labeled amino acids, (R)- and (S)-[(18)F]FAMP 1 and (R)- and (S)-[(18)F]MeFAMP 2 have been prepared and evaluated in vitro and in vivo for their potential utility in brain and systemic tumor imaging based upon primarily system A transport with positron emission tomography (PET).
METHODS
The transport of enantiomers of [(18)F]FAMP 1 and [(18)F]MeFAMP 2 was measured through in vitro uptake assays in human derived cancer cells including A549 (lung), DU145 (prostate), SKOV3 (ovary), MDA MB468 (breast) and U87 (brain) in the presence and absence of amino acid transporter inhibitors. The in vivo biodistribution of these tracers was evaluated using tumor mice xenografts at 15, 30, 60 and 120 min post injection.
RESULTS
All four tracers showed moderate to high levels of uptake (1-9%ID/5×10(5) cells) by the cancer cell lines tested in vitro. AAT cell inhibition assays demonstrated that (R)-[(18)F]1 and (S)-[(18)F]1 entered these tumor cells via mixed AATs, likely but not limited to system A and system L. In contrast, (R)-[(18)F]2 and (S)-[(18)F]2 showed high selectivity for system A AAT. Similar to the results of in vitro cell studies, the tumor uptake of all four tracers was good to high and persisted over the 2 hours time course of in vivo studies. The accumulation of these tracers was higher in tumor than most normal tissues including blood, brain, muscle, bone, heart, and lung, and the tracers with the highest in vitro selectivity for system A AAT generally demonstrated the best tumor imaging properties. Higher uptake of these tracers was observed in the pancreas, kidney and spleen compared to tumors.
CONCLUSIONS
These preclinical studies demonstrate good imaging properties in a wide range of tumors for all four amino acids evaluated with (R)-[(18)F]2 having the highest selectivity for system A AAT.
Topics: Amino Acids, Branched-Chain; Aminoisobutyric Acids; Animals; Biological Transport; Brain; Cell Line, Tumor; Humans; Mice; Positron-Emission Tomography; Propionates; Stereoisomerism
PubMed: 25263130
DOI: 10.1016/j.nucmedbio.2014.07.002 -
PloS One 2014Alterations in the composition of the gut microbiome and/or immune system function may have a role in the development of autism spectrum disorders (ASD). The current...
Pre- and neonatal exposure to lipopolysaccharide or the enteric metabolite, propionic acid, alters development and behavior in adolescent rats in a sexually dimorphic manner.
Alterations in the composition of the gut microbiome and/or immune system function may have a role in the development of autism spectrum disorders (ASD). The current study examined the effects of prenatal and early life administration of lipopolysaccharide (LPS), a bacterial mimetic, and the short chain fatty acid, propionic acid (PPA), a metabolic fermentation product of enteric bacteria, on developmental milestones, locomotor activity, and anxiety-like behavior in adolescent male and female offspring. Pregnant Long-Evans rats were subcutaneously injected once a day with PPA (500 mg/kg) on gestation days G12-16, LPS (50 µg/kg) on G15-16, or vehicle control on G12-16 or G15-16. Male and female offspring were injected with PPA (500 mg/kg) or vehicle twice a day, every second day from postnatal days (P) 10-18. Physical milestones and reflexes were monitored in early life with prenatal PPA and LPS inducing delays in eye opening. Locomotor activity and anxiety were assessed in adolescence (P40-42) in the elevated plus maze (EPM) and open-field. Prenatal and postnatal treatments altered behavior in a sex-specific manner. Prenatal PPA decreased time spent in the centre of the open-field in males and females while prenatal and postnatal PPA increased anxiety behavior on the EPM in female rats. Prenatal LPS did not significantly influence those behaviors. Evidence for the double hit hypothesis was seen as females receiving a double hit of PPA (prenatal and postnatal) displayed increased repetitive behavior in the open-field. These results provide evidence for the hypothesis that by-products of enteric bacteria metabolism such as PPA may contribute to ASD, altering development and behavior in adolescent rats similar to that observed in ASD and other neurodevelopmental disorders.
Topics: Animals; Anxiety; Behavior, Animal; Child Development Disorders, Pervasive; Enterobacteriaceae; Female; Growth and Development; Linear Models; Lipopolysaccharides; Locomotion; Male; Maze Learning; Pregnancy; Prenatal Exposure Delayed Effects; Propionates; Rats; Rats, Long-Evans; Sex Characteristics
PubMed: 24466331
DOI: 10.1371/journal.pone.0087072 -
Microbial Biotechnology Feb 2024Biopreservation refers to the use of natural or controlled microbial single strains or consortia, and/or their metabolites such as short-chain carboxylic acids (SCCA),...
Biopreservation refers to the use of natural or controlled microbial single strains or consortia, and/or their metabolites such as short-chain carboxylic acids (SCCA), to improve the shelf-life of foods. This study aimed at establishing a novel Lactobacillaceae-driven bioprocess that led to the production of the SCCA propionate through the cross-feeding on 1,2-propanediol (1,2-PD) derived from the deoxyhexoses rhamnose or fucose. When grown as single cultures in Hungate tubes, strains of Lacticaseibacillus rhamnosus preferred fucose over rhamnose and produced 1,2-PD in addition to lactate, acetate, and formate, while Limosilactobacillus reuteri metabolized 1,2-PD into propionate, propanol and propanal. Loigolactobacillus coryniformis used fucose to produce 1,2-PD and only formed propionate when supplied with 1,2-PD. Fermentates collected from batch fermentations in bioreactor using two-strain consortia (L. rhamnosus and L. reuteri) or fed-batch fermentations of single strain cultures of L. coryniformis with rhamnose contained mixtures of SCCA consisting of mainly lactate and acetate and also propionate. Synthetic mixtures that contained SCCA at concentrations present in the fermentates were more antimicrobial against Salmonella enterica if propionate was present. Together, this study (i) demonstrates the potential of single strains and two-strain consortia to produce propionate in the presence of deoxyhexoses extending the fermentation metabolite profile of Lactobacillaceae, and (ii) emphasizes the potential of applying propionate-containing fermentates as biopreservatives.
Topics: Propionates; Lactobacillaceae; Rhamnose; Fucose; Fermentation; Acetates; Lactates
PubMed: 38380951
DOI: 10.1111/1751-7915.14392 -
Journal of Dairy Science Jun 2017The objective of this study was to determine the effects of anaplerosis of the tricarboxylic acid cycle on feeding behavior and energy intake of cows in the postpartum...
The objective of this study was to determine the effects of anaplerosis of the tricarboxylic acid cycle on feeding behavior and energy intake of cows in the postpartum period. We infused propionic acid (PA) and glycerol (GL) continuously into the abomasum and hypothesized that PA will decrease meal size and energy intake compared with GL because PA enters the tricarboxylic acid cycle, likely stimulating oxidation of acetyl CoA and satiety compared with GL. Three experiments (Exp.) were conducted using 20 Holstein cows between 3 and 22 d postpartum (8 cows in Exp. 1 and 6 cows each for Exp. 2 and 3). Treatments were compared using isoenergetic (Exp. 1, 193 kcal/h) and isomolar (Exp. 2, ∼0.5 mol/h) continuous infusions of PA (99.5%) and GL (99.7%) to the abomasum using a double crossover design with four 2-d infusion periods each, and 2 mol of PA or GL pulse-dosed to the abomasum using a crossover design (Exp. 3). Treatment sequences were assigned alternately to cows based upon date of parturition. Feeding behavior was recorded by a computerized data acquisition system for Exp. 1 and 2. Propionic acid decreased dry matter intake (DMI) compared with GL 16.7 and 23.4% in Exp. 1 and 2, respectively. The decrease in DMI was because PA decreased meal size compared with GL by 12.6 and 15.3% in Exp. 1 and 2, respectively. Propionic acid decreased total metabolizable energy intake (diet plus treatment infusions) compared with GL for both experiments. Compared with PA, GL increased plasma glucose and insulin concentrations for Exp. 2 only. In Exp. 3, PA decreased hepatic acetyl CoA content 34%, whereas GL increased hepatic acetyl CoA content 32%, resulting in lower hepatic acetyl CoA content for PA compared with GL at 30 min (18.0 vs. 36.9 nmol/g), which persisted at 60 min after dosing (21.9 vs. 32.8 nmol/g). Consistent with our hypothesis, the obligatory anaplerotic metabolite PA decreased meal size, DMI, and total metabolizable energy intake compared with GL, likely because of differences in their hepatic metabolism.
Topics: Abomasum; Acetyl Coenzyme A; Animals; Blood Glucose; Cattle; Citric Acid Cycle; Cross-Over Studies; Eating; Energy Intake; Feeding Behavior; Female; Glycerol; Insulin; Lactation; Liver; Postpartum Period; Pregnancy; Propionates; Satiation
PubMed: 28342606
DOI: 10.3168/jds.2016-12104