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At least 217 records · Page 12Linked to original sources
PubMed1996

Phosphorylation-independent bacterial chemoresponses correlate with changes in the cytoplasmic level of fumarate.

Bacterial chemotaxis is based on modulation of the probability to switch the direction of flagellar rotation. Responses to many stimuli are transduced by a two-component system via reversible phosphorylation of CheY, a small cytoplasmic protein that directly interacts with the switch complex at the flagellar motor. We found that the chemorepellents indole and benzoate induce motor switching in Escherichia coli cells with a disabled phosphorylation cascade. This phosphorylation-independent chemoresponse is explained by reversible inhibition of fumarase by indole or benzoate which leads to an increased level of cellular fumarate, a compound involved in motor switching for bacteria and archaea. Genetic deletion of fumarase increased the intracellular concentration of fumarate and enhanced the switching frequency of the flagellar motors irrespective of the presence or absence of the phosphorylation cascade. These correlations provide evidence for fumarate-dependent metabolic signal transduction in bacterial chemosensing.

Bacterial Proteins↗
PubMed1990

Signal transduction in Halobacterium depends on fumarate.

The isolation of a straight-swimming mutant of Halobacterium halobium is reported which has a defect in switching the rotational sense of its flagellar motor. Cells of this mutant strain could be complemented with an extract from wild-type cells by mild sonication and resealing of the cells in fresh medium. The switch factor responsible for restoration of wild-type behaviour was isolated from membrane vesicle preparations. Its chemical nature is proposed to be that of fumarate on the basis of chemical, chromatographic and mass spectrometric analysis. Since the switch factor (fumarate) was released from a membrane-bound state by heat and was accumulated into mutant cells that lack this compound, it is proposed that a membrane-bound protein exists which specifically binds the switch factor. Both the switch factor and fumarate cause stimulus-induced responses in cells at the level of one or few molecules.

Cell Movement↗
PubMed1977

Anaerobic growth of Escherichia coli on formate by reduction of nitrate, fumarate, and trimethylamine N-oxide.

Anaerobic growth of E. coli, strain K-10, depending on formate oxidation by nitrate, fumarate, and trimethylamine N-oxide was followed in a medium containing peptone. The presence of formate and peptone was indispensable for growth with fumarate and trimethylamine N-oxide reduction. While there was no growth in the absence of acceptor, growth was observed in the absence of formate by nitrate reduction though not as much as under aerobic conditions. Per mole consumed formate equimolar succinate or trimethylamine was formed, but 1.2 mole of nitrate was produced, probably depending partly on peptone oxidation. The molar growth yield on formate was found to be 6.5, 7.6, and 7.0 g cells/mole depending on the reduction of nitrate, fumarate, and trimethylamine N-oxide, respectively, suggesting the formation of one mole ATP coupled to the anaerobic electron transfers from formate.

Aerobiosis↗
PubMed1992

An Escherichia coli mutant containing only demethylmenaquinone, but no menaquinone: effects on fumarate, dimethylsulfoxide, trimethylamine N-oxide and nitrate respiration.

The mutant strain AN70 (ubiE) of Escherichia coli which is known to lack ubiquinone (Young IG et al. 1971), was analyzed for menaquinone (MK) and demethylmenaquinone (DMK) contents. In contrast to the wild-type, strain AN70 contained only DMK, but no MK. The mutant strain was able to grow with fumarate, trimethylamine N-oxide (TMAO) and dimethylsulfoxide (DMSO), but not with nitrate as electron acceptor. The membranes catalyzed anaerobic respiration with fumarate and TMAO at 69 and 74% of wild-type rates. DMSO respiration was reduced to 38% of wild-type activities and nitrate respiration was missing (less than or equal to 8% of wild-type), although the respective enzymes were present in wild-type rates. The results complement earlier findings which demonstrated a role for DMK only in TMAO respiration (Wissenbach et al. 1990). It is concluded, that DMK (in addition to MK) can serve as a redox mediator in fumarate, TMAO and to some extent in DMSO respiration, but not in nitrate respiration. In strain AN70 (ubiE) the lack of ubiquinone (Q) is due to a defect in a specific methylation step of Q biosynthesis. Synthesis of MK from DMK appears to depend on the same gene (ubiE).

Anaerobiosis↗
PubMed1983

Structural properties of the proteoliposomes catalyzing electron transport from formate to fumarate.

The electron-transport chain catalyzing fumarate reduction by formate has recently been reconstituted from the formate dehydrogenase complex and the fumarate reductase complex from Vibrio succinogenes, in a liposomal preparation containing vitamin K-1 (Unden, G. and Kröger, A. (1982) Biochim. Biophys. Acta 682, 258-263). We have now investigated the structural properties of this preparation. The preparation was found to consist of a homogeneous population of unilamellar proteoliposomes with an average diameter of about 100 nm and an internal volume of 2-4 ml/g phospholipid. The buoyant density (1.07 g/ml) was consistent with the protein/phospholipid ratio (0.2 g/g) of the preparation. Leakage of glucose from the internal spaces of the proteoliposomes was negligibly slow. Proteoliposomes prepared with either of the enzyme complexes showed peripheral projections mainly on the outer surface, when examined by electron microscopy after negative staining. The size, orientation and surface density of the projections were consistent with those of the enzymes. Most of the substrate and dye-reactive sites (70-90%) of the enzymes in the proteoliposomes were accessible to external non-permeant substrates. The proteoliposomes catalyzing electron transport were formed by freeze-thawing a mixture of liposomes and protein-phospholipid complexes which did not perform electron transport from formate to fumarate. Nearly the entire amount of the enzymes supplied (0.2 g protein/g phospholipid) was incorporated into the liposomes by this procedure. The transformation of liposomes into proteoliposomes was accompanied by exchange of the internal solutes with the external medium.

Aldehyde Oxidoreductases↗
PubMed1983

Fumaric aciduria: a new organic aciduria, associated with mental retardation and speech impairment.

Two siblings are described who present with fumaric aciduria, a hitherto unreported organic aciduria. The results of our analytical investigations using gas chromatography/mass spectrometry, and the clinical presentation of the patients, are consistent with the notion that the fumaric aciduria is caused by an inherited defect which leads to a net secretion of fumaric acid by the renal tubules.

Adult↗
PubMed2000

Voltammetry of a flavocytochrome c(3): the lowest potential heme modulates fumarate reduction rates.

Iron-induced flavocytochrome c(3), Ifc(3), from Shewanella frigidimarina NCIMB400, derivatized with a 2-pyridyl disulfide label, self-assembles on gold electrodes as a functional array whose fumarate reductase activity as viewed by direct electrochemistry is indistinguishable from that of Ifc(3) adsorbed on gold or graphite electrodes. The enhanced stability of the labeled protein's array permits analysis at a rotating electrode and limiting catalytic currents fit well to a Michaelis-Menten description of enzyme kinetics with K(M) = 56 +/- 20 microM, pH 7.5, comparable to that obtained in solution assays. At fumarate concentrations above 145 microM cyclic voltammetry shows the catalytic response to contain two features. The position and width of the lower potential component centered on -290 mV and corresponding to a one-electron wave implicates the oxidation state of the lowest potential heme of Ifc(3) as a defining feature in the mechanism of fumarate reduction at high turnover rates. We propose the operation of dual pathways for electron transfer to the active site of Ifc(3) with the lowest potential heme acting as an electron relay on one of these pathways.

Binding Sites↗
PubMed1997

Identification of the yeast ACR1 gene product as a succinate-fumarate transporter essential for growth on ethanol or acetate.

The protein encoded by the ACR1 gene in Saccharomyces cerevisiae belongs to a family of 35 related membrane proteins that are encoded in the fungal genome. Some of them are known to transport various substrates and products across the inner membranes of mitochondria, but the functions of 28 members of the family are unknown. The yeast ACR1 gene was introduced into Escherichia coli on an expression plasmid. The protein was over-produced as inclusion bodies, which were purified and solubilised in the presence of sarkosyl. The solubilised protein was reconstituted into liposomes and shown to transport fumarate and succinate. Its physiological role in S. cerevisiae is probably to transport cytoplasmic succinate, derived from isocitrate by the action of isocitrate lyase in the cytosol, into the mitochondrial matrix in exchange for fumarate. This exchange activity and the subsequent conversion of fumarate to oxaloacetate in the cytosol would be essential for the growth of S. cerevisiae on ethanol or acetate as the sole carbon source.

Acetates↗
PubMed1989

Systemic therapy with fumaric acid derivates: new possibilities in the treatment of psoriasis.

For the past two decades fumaric acid (FA) therapy has become an increasingly popular treatment in Western Europe for psoriasis. FA therapy originally was developed by Schweckendiek and subsequently standardized by Schäfer. Schäfer's fumaric acid compound therapy (FACT) consists of the oral intake of dimethylfumaric acid ester (DMFAE) and several salts of monoethylfumaric acid ester (MEFAE) in combination with topical fumaric acid therapy (1% to 3% MEFAE in an ointment or FA in bathing oils) and a diet. Schäfer claimed excellent results in a large number of patients. Preliminary studies by German dermatologists, however, revealed contradictory therapeutic results and serious side effects, and FA treatment was soon abandoned by dermatologists. To assess the value of FA therapy we conducted an open pilot study of 36 patients in which FACT therapy appeared to be rather effective. Thereafter, several controlled studies with MEFAE sodium in two different dosages versus placebo, and DMFAE versus placebo, were done. The results indicated that MEFAE sodium in dosages up to 240 mg daily was ineffective, whereas daily dosages of 720 mg resulted in a significant decrease in scaling and itching but did not affect extension of the eruption. DMFAE, 240 mg daily, produced a significant amelioration and prevented extension. Side effects of FA treatment were nausea, diarrhea, general malaise, and severe stomachache. Mild disturbances of liver and kidney function during treatment were observed with the 720 mg dosage of MEFAE and with the 240 mg dosage of DMFAE. Moreover, a relative lymphopenia with a selective decrease of suppressor T lymphocytes occurred in about 50% of the patients treated with DMFAE.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2001

Modification of oligo(poly(ethylene glycol) fumarate) macromer with a GRGD peptide for the preparation of functionalized polymer networks.

A novel macromer, oligo(poly(ethylene glycol) fumarate) (OPF), was synthesized by the reaction between poly(ethylene glycol) (PEG) of molecular weight 1000 (PEG 1.0K) and fumaryl chloride. The oligo(PEG fumarate) (OPF 1.0K) was modified with a peptide known to modulate cellular functions, Gly-Arg-Gly-Asp (GRGD), after being activated with 4-nitrophenyl chloroformate (NPC). The determined yield of the GRGD modification in 0.1 M sodium bicarbonate buffer of pH 8.3 was 83% as determined by NMR measurements. The OPF 1.0K and the OPF 1.0K modified with GRGD were cross-linked with an unsaturated biodegradable polyester, poly(propylene fumarate) (PPF), by photopolymerization. The cross-linked PPF was characterized by Fourier transform infrared (FT-IR) spectroscopy and contact angle measurements. The equilibrium contact angle of water on the cross-linked PPF surface decreased with the incorporation of OPF 1.0K and the OPF 1.0K modified with GRGD. The results suggest that the OPF macromer can be used for the preparation of functionalized networks incorporating cell adhesion specific sequences.

Biopolymers↗
PubMedDate not supplied

Photoinitiated cross-linking of the biodegradable polyester poly(propylene fumarate). Part I. Determination of network structure.

In this work, we investigated the mechanism involved in the photoinitiated cross-linking of the polyester poly(propylene fumarate) (PPF) using the initiator bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide (BAPO). It was hypothesized that BAPO has the ability to cross-link PPF into solid polymer networks, without the use of a cross-linking monomer, because two pairs of radicals, both involving a fast adding phosphinoyl radical, were formed upon UV irradiation of BAPO. Spectroscopic investigation first confirmed the addition of BAPO derived radicals to the PPF olefin. Investigations of fumarate conversion and bulk network properties were then undertaken, using the BAPO initiator and a monoacylphosphine oxide (MAPO) initiator which contains a single photolabile bond. Results show that a single BAPO phosphinoyl radical was primarily responsible for the formation of a highly cross-linked PPF network and the additional radical pair which may be formed does not dramatically alter fumarate conversion or bulk network properties. From these results, the network structure of BAPO initiated, photo-cross-linked PPF may be deduced. Finally, this study demonstrates a method for inferring cross-linked network structures by contrasting properties of bulk materials formed from similar cross-linking initiators.

Biocompatible Materials↗
PubMed1999

Open conformation of a flavocytochrome c3 fumarate reductase.

Fumarate reductases and succinate dehydrogenases play central roles in the metabolism of eukaryotic and prokaryotic cells. A recent medium resolution structure of the Escherichia coli fumarate reductase (Frd) has revealed the overall organization of the membrane-bound complex. Here we present the first high resolution X-ray crystal structure of a water-soluble bacterial fumarate reductase in an open conformation. This structure reveals a mobile domain that modulates substrate access to the active site and provides new insights into the mechanism of this widespread and important family of FAD-containing respiratory proteins.

Amino Acid Sequence↗
PubMed1999

Structural and mechanistic mapping of a unique fumarate reductase.

The 1.8 A resolution crystal structure of the tetraheme flavocytochrome c3, Fcc3, provides the first mechanistic insight into respiratory fumarate reductases or succinate dehydrogenases. The multi-redox center, three-domain protein shows a 40 A long 'molecular wire' allowing rapid conduction of electrons through a new type of cytochrome domain onto the active site flavin, driving the reduction of fumarate to succinate. In this structure a malate-like molecule is trapped in the enzyme active site. The interactions between this molecule and the enzyme suggest a clear mechanism for fumarate reduction in which the substrate is polarized and twisted, facilitating hydride transfer from the reduced flavin and subsequent proton transfer. The enzyme active site in the oxidized form is completely buried at the interface between the flavin-binding and the clamp domains. Movement of the cytochrome and clamp domains is postulated to allow release of the product.

Amino Acid Sequence↗
PubMed1976

Effects of dicyclohexylcarbodi-imide on proton translocation coupled to fumarate reduction in anaerobically grown cells of Escherichia coli K-12.

The addition of dicyclohexylcarbodi-imide to anaerobic cells of Escherichia coli K12 decreases both the observed extent of proton translocation coupled to fumarate reduction by endogenous substrates and the t 1/2 of proton re-entry after such translocation, but does not affect fumarate uptake. Dicyclohexylcarbodi-imide also inhibits fumarate reductase activity in cell extracts.

Anaerobiosis↗
PubMed1977

Proton translocation coupled to electron flow from endogenous substrates to fumarate in anaerobically grown Escherichia coli K12.

Observed leads to H+/2e- values for proton translocation during the reduction of fumarate by endogenous substrates in anaerobic cells of Escherichia coli K12 varied with fumarate concentration. This variation was probably due mainly to incomplete fumarate utilization. Under optimum conditions a minimum value for leads to H+/2e- of 1.04+/-0.20 was obtained.

Anaerobiosis↗
PubMed1979

Properties and function of fumarate reductase (NADH) in Streptococcus lactis.

The fumarate reductase (NADH) present in cell-free extracts of S. lactis C10 was purified approximately 100-fed by chromatography on DEAE-cellulose in the presence of the non-ionic detergent Teric X-10, and some of the properties of this partially purified enzyme were characterized. Fumarate was able to act as a terminal electron acceptor and decreased the amount of lactate formed and oxygen used during the metabolism of pyruvate by resting cells of S. lactis. Anaerobic growth of S. lactis on glycerol was not observed and fumarate reduction was not coupled with glycerol-3-phosphate oxidation.

Anaerobiosis↗
PubMed1996

Molecular characterization of potato fumarate hydratase and functional expression in Escherichia coli.

The tricarboxylic acid cycle enzyme fumarase (fumarate hydratase; EC 4.2.1.2) catalyzes the reversible hydration of fumarate to L-malate. We report the molecular cloning of a cDNA (StFum-1) that encodes fumarase from potato (Solanum tuberosum L.). RNA blot analysis demonstrated that StFum-1 is most strongly expressed in flowers, immature leaves, and tubers. The deduced protein contains a typical mitochondrial targeting peptide and has a calculated molecular mass of 50.1 kD (processed form). Potato fumarase complemented a fumarase-deficient Escherichia coli mutation for growth on minimal medium that contains acetate or fumarate as the sole carbon source, indicating that functional plant protein was produced in the bacterium. Antiserum raised against the recombinant plant enzyme recognized a 50-kD protein in wild-type but not in StFum-1 antisense plants, indicating specificity of the immunoreaction. A protein of identical size was also detected in isolated potato tuber mitochondria. Although elevated activity of fumarase was previously reported for guard cells (as compared with mesophyll cells), additional screening and genomic hybridization data reported here do not support the hypothesis that a second fumarase gene is expressed in potato guard cells.

Amino Acid Sequence↗
PubMed2002

Fumarate-mediated inhibition of erythrose reductase, a key enzyme for erythritol production by Torula corallina.

Torula corallina, a strain presently being used for the industrial production of erythritol, has the highest erythritol yield ever reported for an erythritol-producing microorganism. The increased production of erythritol by Torula corallina with trace elements such as Cu(2+) has been thoroughly reported, but the mechanism by which Cu(2+) increases the production of erythritol has not been studied. This study demonstrated that supplemental Cu(2+) enhanced the production of erythritol, while it significantly decreased the production of a major by-product that accumulates during erythritol fermentation, which was identified as fumarate by instrumental analyses. Erythrose reductase, a key enzyme that converts erythrose to erythritol in T. corallina, was purified to homogeneity by chromatographic methods, including ion-exchange and affinity chromatography. In vitro, purified erythrose reductase was significantly inhibited noncompetitively by increasing the fumarate concentration. In contrast, the enzyme activity remained almost constant regardless of Cu(2+) concentration. This suggests that supplemental Cu(2+) reduced the production of fumarate, a strong inhibitor of erythrose reductase, which led to less inhibition of erythrose reductase and a high yield of erythritol. This is the first report that suggests catabolite repression by a tricarboxylic acid cycle intermediate in T. corallina.

Aldehyde Reductase↗