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PubMed2004

Fumaric acid in apple juice: a potential indicator of microbial spoilage of apples used as raw material.

The effects of heat treatment (evaporation and excessive heating), and microbial contamination (Rhizopus stolonifer, Penicillium expansum and Lactobacillus plantarum) as sources of fumaric acid formation in apple juice concentrates were investigated. Fumaric acid formed in apple juice did not exceed 1.0 mg l(-1) during both commercial-scale evaporation and laboratory-scale excessive heat treatment, indicating that malic dehydration is not the primary source of fumaric acid formation. However, R. stolonifer and L. plantarum produced 18.23 +/- 0.82 and 5.39 +/- 0.31 mg l(-1) fumaric acid as determined in the raw juice obtained from contaminated apples after 5 days of incubation. The mean fumaric acid content of apple juice concentrates manufactured in 2000, 2001 and 2002 were determined as 4.9 +/- 1.9, 5.7 +/- 2.8 and 4.1 +/- 2.6 mg l(-1), respectively. The overall results suggest that the primary source of fumaric acid in apple juice concentrate is the use of apples decayed by certain microorganisms capable of producing fumaric acid.

Beverages↗
PubMed1997

Requirement for the proton-pumping NADH dehydrogenase I of Escherichia coli in respiration of NADH to fumarate and its bioenergetic implications.

In Escherichia coli the expression of the nuo genes encoding the proton pumping NADH dehydrogenase I is stimulated by the presence of fumarate during anaerobic respiration. The regulatory sites required for the induction by fumarate, nitrate and O2 are located at positions around -309, -277, and downstream of -231 bp, respectively, relative to the transcriptional-start site. The fumarate regulator has to be different from the O2 and nitrate regulators ArcA and NarL. For growth by fumarate respiration, the presence of NADH dehydrogenase I was essential, in contrast to aerobic or nitrate respiration which used preferentially NADH dehydrogenase II. The electron transport from NADH to fumarate strongly decreased in a mutant lacking NADH dehydrogenase I. The mutant used acetyl-CoA instead of fumarate to an increased extent as an electron acceptor for NADH, and excreted ethanol. Therefore, NADH dehydrogenase I is essential for NADH-->fumarate respiration, and is able to use menaquinone as an electron acceptor. NADH-->dimethylsulfoxide respiration is also dependent on NADH dehydrogenase I. The consequences for energy conservation by anaerobic respiration with NADH as a donor are discussed.

Acetates↗
PubMed1995

Fumarate hydration test for differentiation of Campylobacter and Helicobacter species.

A total of 65 Campylobacter and Helicobacter strains comprising 15 species were tested for fumarate hydration by using a rapid high-performance liquid chromatographic (HPLC) method. All strains of C. jejuni, C. coli, C. jejuni subsp. doylei, C. fetus, C. hyointestinalis, C. lari, "C. lari variant", C. upsaliensis, H. fennelliae and H. pylori hydrated fumarate, whereas no strains of C. sputorum (all three biovars), H. cinaedi or H. mustelae did. L-malic acid was detected in the supernatant of the cultures of all strains that hydrated fumarate, but not in the culture supernatant of any of the strains that failed to hydrate fumarate. These findings show that all Campylobacter and Helicobacter strains that hydrated fumarate were able to form L-malic acid from fumarate. HPLC determination of organic acid is a rapid method that requires no chemical treatment before analysis. Because it is reproducible, the HPLC fumarate hydration test should be useful as conventional method for identification of Campylobacter and Helicobacter spp.

Campylobacter↗
PubMed1997

Anaerobic activation of toluene and o-xylene by addition to fumarate in denitrifying strain T.

Anaerobic assays conducted with strain T, a denitrifying bacterium capable of mineralizing toluene to carbon dioxide, demonstrated that toluene-grown, permeabilized cells catalyzed the addition of toluene to fumarate to form benzylsuccinate. This reaction was not dependent on the presence of coenzyme A (CoA) or ATP. In the presence of CoA, formation of E-phenylitaconate from benzylsuccinate was also observed. Kinetic studies demonstrated that the specific rate of benzylsuccinate formation from toluene and fumarate in assays with permeabilized cells was >30% of the specific rate of toluene consumption in whole-cell suspensions with nitrate; this observation suggests that benzylsuccinate formation may be the first reaction in anaerobic toluene degradation by strain T. Use of deuterium-labeled toluene and gas chromatography-mass spectrometry indicated that the H atom abstracted from the toluene methyl group during addition to fumarate was retained in the succinyl moiety of benzylsuccinate. In this study, no evidence was found to support previously proposed reactions of toluene with acetyl-CoA or succinyl-CoA. Toluene-grown, permeabilized cells of strain T also catalyzed the addition of o-xylene to fumarate to form (2-methylbenzyl)succinate. o-Xylene is not a growth substrate for strain T, and its transformation was probably cometabolic. With the exception of specific reaction rates, the observed characteristics of the toluene-fumarate addition reaction (i.e., retention of a methyl H atom and independence from CoA and ATP) also apply to the o-xylene-fumarate addition reaction. Thus, addition to fumarate may be a biochemical strategy to anaerobically activate a range of methylbenzenes.

Anaerobiosis↗
PubMed1991

Research note: fumaric acid enhances performance of broiler chickens.

Two studies were conducted to examine the effects of dietary inclusion of fumaric acid on performance and carcass composition of broiler chickens. Fumaric acid was added to nutritionally complete diets at levels of 0, .125, .25, and .5% and fed from 1 to 49 days under simulated commercial conditions. In one trial, samples of birds were processed to determine dressing percentage and abdominal fat content. In the first trial (mixed sex broilers), the addition of .125% fumaric acid significantly (P less than .05) improved 49-day body weight of females and average weight gain of both sexes with no effect on feed utilization. Feed consumption was significantly increased when diets contained .125 or .50% fumaric acid. In the second trial (male broilers), 49-day body weight was significantly (P less than .05) improved by the addition of .125 and .25% fumaric acid. There were no significant differences in feed consumption; feed utilization was improved by the addition of all levels of fumaric acid. Dietary fumaric acid had no adverse effects on dressing percentage, abdominal fat content, or mortality rate.

Animals↗
PubMed2001

Purification and enzymatic activity of an NADH-fumarate reductase and other mitochondrial activities of Leishmania parasites.

A 65 kD membrane-associated NADH-fumarate reductase subunit, which has a molecular weight similar to that of one of the enzyme subunits from bacteria, was purified from Leishmania donovani promastigotes. NADH-fumarate reductase and other mitochondrial enzymatic activities of L. major and L. donovani promastigotes and amastigotes were investigated. The presence of NADH-fumarate reductase was demonstrated in digitonin-permeabilized L. major promastigotes and mitochondria of L. major and L. donovani promastigotes and amastigotes. The activity of solubilized NADH-fumarate reductase was measured in L. major and L. donovani promastigotes. Succinate exhibited a clear concentration-dependent inhibitory effect on fumarate reductase, whereas fumarate also exhibited a clear concentration-dependent inhibitory effect on succinate dehydrogenase. The data indicate that fumarate reductase is an obligatory component of the respiratory chain of the parasite. Since the enzyme is an important component in the intermediate metabolism in the Leishmania parasite and is absent in mammalian cells, it could be a potential target for antileishmanial drugs.

Animals↗
PubMed2025

Regulation of airway fumarate by host and pathogen promotes S. aureus pneumonia.

Staphylococcus aureus is a leading cause of healthcare-associated pneumonia, contributing significantly to morbidity and mortality worldwide. As a ubiquitous colonizer of the upper respiratory tract, S. aureus must undergo substantial metabolic adaptation to achieve persistent infection in the distinctive microenvironment of the lung. We observed that fumC, which encodes the enzyme that converts fumarate to malate, is highly conserved with low mutation rates in S. aureus isolates from chronic lung infections. Fumarate, a pro-inflammatory metabolite produced by macrophages during infection, is regulated by the host fumarate hydratase (FH) to limit inflammation. Here, we demonstrate that fumarate, which accumulates in the chronically infected lung, is detrimental to S. aureus, blocking primary metabolic pathways such as glycolysis and oxidative phosphorylation (OXPHOS). This creates a metabolic bottleneck that drives staphylococcal FH (FumC) activity for airway adaptation. FumC not only degrades fumarate but also directs its utilization into critical pathways including the tricarboxylic acid (TCA) cycle, gluconeogenesis and hexosamine synthesis to maintain metabolic fitness and form a protective biofilm. Itaconate, another abundant immunometabolite in the infected airway enhances FumC activity, in synergy with fumarate. In a mouse model of pneumonia, a ΔfumC mutant displays significant attenuation compared to its parent and complemented strains, particularly in fumarate- and itaconate-replete conditions. Our findings underscore the pivotal role of immunometabolites in promoting S. aureus pulmonary adaptation.

Journal Article↗
PubMed1981

The function of the subunits of the fumarate reductase complex of Vibrio succinogenes.

The membrane-bound fumarate reductase complex of Vibrio succinogenes catalyzes the reduction of fumarate by 2,3-dimethyl-1,4-naphthohydroquinone (dimethylnaphthohydroquinone) and consists of three different peptides (Mr 79,000, Mr 31,000 and Mr 25,000), the smallest of which is cytochrome b [Unden, G., Hackenberg, H. and Kröger A. (1980) Biochem. Biophys. Acta 591, 275-288]. The complex was cleaved with guanidinium chloride, the resulting subunits characterized and their functions within the complex investigated by reconstitutional experiments. 1. The Mr-79,000 subunits catalyzed the reduction of fumarate by benzylviologen radicals as well as the oxidation of succinate by methylene blue, but not fumarate reduction by dimethylnaphthohydroquinone. 2. The spectral and the redox properties of the isolated cytochrome b (Mr 25,000) were equivalent to those of the high-potential cytochrome b of the bacteria. The isolated cytochrome b had a midpoint potential of -15 mV and was reducible by dimethylnaphthohydroquinone in the absence of the other subunits. 3. The Mr-31,000 subunit did not catalyze any of the reactions mentioned above. For the reduction of cytochrome b by succinate in the presence of the Mr-79,000 subunit, an amount of the Mr-31,000 subunit was required which was equimolar to cytochrome b. 4. The activity of fumarate reduction by dimethylnaphthohydroquinone could be restored by coprecipitation of the three subunits. It is concluded that the fumarate reductase complex has two different sites, which are essential for its function in the phosphorylative electron transport of the bacterium. The site reacting with the substrates fumarate and succinate is situated on the Mr-79,000 subunit, and that reacting with dimethylnaphthohydroquinone is cytochrome b. The Mr-31,000 subunit mediates the electron transport between cytochrome b and the Mr-79,000 subunit.

Bacterial Proteins↗
PubMed1984

Overproduction of fumarate reductase in Escherichia coli induces a novel intracellular lipid-protein organelle.

The expression of fumarate reductase in Escherichia coli has been amplified over 30-fold by utilizing a recombinant plasmid, pFR63 , carrying the fumarate reductase operon. More than 50% of the inner-membrane protein could be accounted for by the enzyme, whereas the total amount of protein associated with the membrane fraction doubled. The membrane accommodated this excess fumarate reductase without reducing the levels of other membrane-associated enzymes. At the same time, the amount of membrane lipid increased such that the lipid/protein ratio remained constant, indicating that the total amount of membrane had doubled. Small alterations in fatty acid composition as well as a large increase in cardiolipin were detected in the fumarate reductase-enriched membranes. The excess membrane was localized in novel tubular structures which were observed in thin-section and negatively stained electron-microscopic preparations. The tubules only appeared after the cytoplasmic membrane became highly enriched in fumarate reductase. They branched from the cytoplasmic membrane and were fumarate reductase. They branched from the cytoplasmic membrane and were composed of an aggregate of fumarate reductase and lipid.

Bacterial Proteins↗
PubMed2006

Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children.

OBJECTIVE: Tenofovir disoproxil fumarate, a nucleotide analog HIV reverse transcriptase inhibitor with demonstrated activity against nucleoside-resistant HIV, is approved for use in adults but not children. Metabolic bone abnormalities have been seen in young animals given high-dose tenofovir and HIV-infected adults that were treated with oral tenofovir disoproxil fumarate. However, tenofovir disoproxil fumarate is being used in children despite a lack of bone safety data. We hypothesized that, given the higher rate of bone turnover that is associated with normal skeletal growth, the potential for TDF-related bone toxicity may be greater in children than in adults. METHODS: Fifteen highly antiretroviral-experienced HIV-infected children who were 8 to 16 years of age (mean +/- SD: 12 +/- 2) and required a change in therapy received tenofovir disoproxil fumarate 175 to 300 mg/m2 per day (adult dose equivalent) as part of highly active antiretroviral therapy for up to 96 weeks. Bone mineral density of the lumbar spine, femoral neck, and total hip by dual-energy x-ray absorptiometry and blood and urine markers of bone metabolism were measured at 0, 24, 48, 72, and 96 weeks. RESULTS: Median z score (SD score compared with age, gender, and ethnicity-matched control subjects) of the lumbar spine, femoral neck, and total hip were decreased from baseline at 24 weeks and 48 weeks and then stabilized. Lumbar spine bone mineral apparent density (which estimates volumetric bone mineral density independent of bone size) z scores also decreased at 24 weeks. Absolute decreases in bone mineral density were observed in 6 children; the mean age of these children was significantly younger than the bone mineral density stable group (10.2 +/- 1.1 vs 13.2 +/- 1.8 years). The change in lumbar spine bone mineral density correlated with decreases in HIV plasma RNA during treatment. Metabolic markers of bone formation and resorption were variable. Two children in whom tenofovir disoproxil fumarate was discontinued because of bone loss that exceeded protocol allowances demonstrated partial or complete recovery of bone mineral density by 96 weeks. CONCLUSIONS: Tenofovir disoproxil fumarate use in children seems to be associated with decreases in bone mineral density that, in some children, stabilize after 24 weeks. Increases in bone markers and calcium excretion suggest that tenofovir disoproxil fumarate may stimulate bone resorption. Bone turnover is higher in children than in older adolescents and adults because of skeletal growth, potentially explaining the greater effect seen in young children. Decreases in bone mineral density correlate with decreases in viral load and young age, suggesting that young responders may be at greater risk for bone toxicity.

Adenine↗
PubMed2006

Pharmacokinetics and dosing recommendations of tenofovir disoproxil fumarate in hepatic or renal impairment.

BACKGROUND: Tenofovir disoproxil fumarate is the prodrug of the acyclic nucleotide reverse transcriptase inhibitor tenofovir that is indicated for use in the treatment of HIV. Tenofovir is eliminated as unchanged drug in the urine, with a significant component of active tubular secretion. The aim of this study was to evaluate the pharmacokinetics of tenofovir in subjects with renal or hepatic impairment, both of which are common in HIV-infected individuals. PATIENTS AND METHODS: HIV seronegative and otherwise healthy subjects with varying degrees of renal or hepatic function were recruited, and tenofovir pharmacokinetics were evaluated over 48 hours (hepatic impairment study) and 96 hours (renal impairment study) following a single tenofovir disoproxil fumarate 300 mg dose. Subjects with hepatic dysfunction were categorised based upon Child-Pugh-Turcotte score, and subjects with renal impairment were categorised based upon their calculated creatinine clearance (CL(CR)) using the Cockcroft-Gault method. RESULTS: As expected for a renally eliminated drug, subjects with and without hepatic impairment displayed similar tenofovir systemic exposures without evidence of substantial alterations in drug disposition, and therefore no dosage adjustments were warranted in these patients. In contrast, in subjects with renal impairment, two distinct groups were observed: (i) subjects with CL(CR)>/=50 mL/min in whom tenofovir pharmacokinetics were similar to subjects with normal renal function; and (ii) subjects with CL(CR) <50 mL/min (moderate or severe impairment) in which tenofovir renal clearance was substantially reduced and thus drug exposures increased. Subjects with end-stage renal disease (ESRD) demonstrated no extrarenal route of tenofovir elimination. Simulations of once-daily or modified dosing regimens demonstrated the need for tenofovir disoproxil fumarate dose-interval adjustment to prevent unnecessary drug accumulation. In patients with ESRD, high-flux haemodialysis efficiently removed tenofovir, with an elimination rate of 134 mL/min and an extraction coefficient of 54%. CONCLUSION: No tenofovir disoproxil fumarate dose adjustment is warranted in the setting of hepatic impairment. Tenofovir disoproxil fumarate 300 mg every 48 hours in individuals with moderate renal impairment and twice weekly corresponding to every 72-96 hours in those with severe renal impairment is recommended in order to target steady-state tenofovir exposures consistent with those observed in subjects with normal renal function receiving tenofovir disoproxil fumarate 300 mg once daily. For subjects receiving thrice-weekly 4-hour maintenance haemodialysis sessions, tenofovir disoproxil fumarate 300 mg administered every 7 days after a haemodialysis session is recommended. HIV-infected patients with significant end-organ dysfunction should be monitored in accordance with clinical practice, including close management of their viral suppression and clinical chemistries.

Adenine↗
PubMed2004

Emtricitabine/tenofovir disoproxil fumarate.

Gilead Sciences is developing a fixed-dose co-formulation of two of its reverse transcriptase inhibitors, emtricitabine [Emtriva] and tenofovir disoproxil fumarate [Viread], for once-daily dosing in combination with other antiretrovirals for the treatment of HIV infection. Each co-formulated tablet will contain 300 mg of tenofovir disoproxil fumarate and 200 mg of emtricitabine. Emtricitabine [Emtriva] is a nucleoside reverse transcriptase inhibitor (NRTI) with demonstrated potent activity against HIV and hepatitis B virus (HBV). It was first approved in the US by the FDA in July 2003 and is indicated for adults aged > or =18 years. Safety and effectiveness in paediatric patients have not been established. In antiretroviral-treatment-experienced patients, the use of emtricitabine may be considered for adults with HIV strains that are expected to be susceptible to the drug as assessed by genotypic or phenotypic testing. The recommended dose of emtricitabine is one 200 mg capsule daily, with or without food. In the European Union, emtricitabine is indicated in combination with other antiretroviral agents for the treatment of HIV in adults and children, where it is also licensed as an oral 10 mg/mL solution. The oral solution is for use in infants older than 4 months, children and patients unable to swallow hard capsules, and patients with renal impairment who require dose reduction. Tenofovir disoproxil fumarate [Viread] is a nucleotide reverse transcriptase inhibitor that is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced patients. The drug was first approved in the US in October 2001, followed by further approvals in the European Union, Australia, Iceland, Brazil, Canada and Switzerland. The drug has been launched in all these countries. In February 2003, the EMEA's advisory committee adopted a positive opinion to extend the indication of tenofovir disoproxil fumarate in all 15 member states to include the product's use in antiretroviral-naïve HIV-infected patients. In July 2003, Japan Tobacco signed an agreement with Gilead for the commercialisation of tenofovir disoproxil fumarate and emtricitabine and the future co-formulation of these two drugs within Japan. Under the terms of the agreement, Japan Tobacco will be submitting an application to the Japanese Ministry of Health, Labour and Welfare for regulatory approval of tenofovir disoproxil fumarate and emtricitabine. On 15 March 2004, Gilead announced the submission of a New Drug Application (NDA) to the US FDA and a Marketing Authorisation Application (MAA) to the EMEA for marketing approval of the fixed-dose co-formulation of emtricitabine and tenofovir disoproxil fumarate. The MAA will be reviewed under the centralised procedure, which, when finalised, will provide one marketing authorisation in all 25 member states of the enlarged European Union. Gilead anticipates launching the combination pill on the US market early in 2005. Regulatory filings for marketing approval in Japan by Japan Tobacco are also expected during 2004. In August 2003, Gilead announced that enrollment had begun in a 48-week phase III study (Study 934) evaluating the efficacy of a once-daily regimen of Viread and Emtriva versus Combivir. The open-label, multicentre trial will enroll up to 500 treatment-naive, HIV-infected patients in the US and Europe. Patients in one arm will receive Viread 300 mg, Emtriva 200mg and efavirenz 600 mg once daily. Patients in the comparator arm will receive Combivir) (lamivudine 150 mg/zidovudine 300 mg) twice daily and efavirenz 600 mg once daily.

Adenine↗
PubMed2000

Atypical antipsychotic effects of quetiapine fumarate in animal models.

AIM: To evaluate the effect of quetiapine fumarate in animal models of schizophrenia and its possibility to induce extrapyramidal side effects (EPSE). METHODS: The enhancement of immobility in a forced swimming test of mice induced by repeated treatment with phencyclidine and amphetamine swimming "normalization" test of mice were used as animal models of negative and positive symptoms of schizophrenia, respectively. The paw test of rats was used to evaluate the possibility by quetiapine fumarate to induce EPSE. RESULTS: After treatment with phencyclidine (10 mg.kg-1.d-1, s.c., 14 d), the immobility time in the forced swimming test of mice was increased (P < 0.01). Quetiapine fumarate (20, 40, and 80 mg.kg-1, ig) and clozapine (10 and 30 mg.kg-1, ig) attenuated the enhanced immobility in the forced swimming test induced by repeated treatment with phencyclidine (P < 0.01), whereas haloperidol (0.3 and 1 mg.kg-1, ig) had no effect. In amphetamine swimming "normalization" test, quetiapine fumarate ameliorated the disorder induced by amphetamine in a dose-dependent manner. In paw test, quetiapine fumarate was much less effective in increasing the forelimb retraction time (FRT) than the hindlimb retraction time (HRT). The minimal effective dose (MED) of HRT (MEDHRT) and FRT (MEDFRT) of quetiapine fumarate was 20 mg.kg-1 and 100 mg.kg-1, respectively, and the ratio of MEDFRT to MEDHRT was 5. CONCLUSION: The effects of quetiapine fumarate in these models indicated its clinical effect on schizophrenia with a reduced liability to produce EPSE.

Amphetamine↗
PubMed1978

Fumarate reductase of Clostridium formicoaceticum. A peripheral membrane protein.

When Clostridium formicoaceticum was grown on fumarate or L-malate crude cell extracts contained a high fumarate reductase activity. Using reduced methyl viologen as electron donor the specific activity amounted to 2-3.5 U per mg of protein. Reduced benzyl viologen, FMNH2 and NADH could also serve as electron donors but the specific activities were much lower. The NADH-dependent activity was strictly membrane-bound and rather labile. Its specific activity did not exceed 0.08 U per mg of particle protein. Fumarate reductase activity was also found in cells of C. formicoaceticum grown on fructose, gluconate, glutamate and some other substrates. The methyl viologen-dependent fumarate reductase activity could almost completely be measured with intact cells whereas only about 25% of the cytoplasmic acetate kinase activity was detected with cell suspensions. The preparation of spheroplasts from cells of C. formicoaceticum in 20 mM HEPES-KOH buffer containing 0.6 M sucrose and 1 mM dithioerythritol resulted in the specific release of 88% of the fumarate reductase activity into the spheroplast medium. Only small amounts of the cytoplasmic proteins malic enzyme and acetate kinase were released during this procedure. There results indicate a peripheral location of the fumarate reductase of C. formicoaceticum on the membrane.

Acetate Kinase↗
PubMed1987

Anion transport in rat brain mitochondria: fumarate uptake via the dicarboxylate carrier.

Penetration of fumarate into rat brain mitochondria has been investigated, as required in brain ammoniogenesis. Mitochondria swell in ammonium fumarate and this swelling is increased by both Pi and malate. According to a carrier mediated process, fumarate translocation, which occurs in exchange with intramitochondrial malate or Pi shows saturation characteristics. By photometrically investigating the kinetics of fumarate/malate, fumarate/Pi and malate/Pi exchanges, different Km values were obtained (10, 22 and 250 microM, respectively), whereas no significant difference was found for Vmax values (40 nmol NAD(P)+ reduced/min X mg protein). This suggests that fumarate and malate share a single carrier to enter mitochondria, namely the dicarboxylate carrier. Both comparison made of the Vmax values and inhibition studies exclude a fumarate translocation via either the tricarboxylate carrier, whose occurrence in brain is here demonstrated, or oxodicarboxylate carrier. Kinetic investigation of the dicarboxylate translocator shows the existence of thiol group/s and metal ion/s at or near the substrate binding sites. The experimental findings are discussed in the light of fumarate uptake in vivo in brain ammoniogenesis.

Animals↗
PubMed1998

Two membrane anchors of Wolinella succinogenes hydrogenase and their function in fumarate and polysulfide respiration.

Wolinella succinogenes can grow by anaerobic respiration with fumarate or polysulfide as the terminal electron acceptor, and H2 or formate as the electron donor. A DeltahydABC mutant lacking the hydrogenase structural genes did not grow with H2 and either fumarate or polysulfide. In contrast to the wild-type strain, the mutant grown with fumarate and with formate instead of H2 did not catalyze the reduction of fumarate, polysulfide, dimethylnaphthoquinone, or benzyl viologen by H2. Growth and enzymic activities were restored upon integration of a plasmid carrying hydABC into the genome of the DeltahydABC mutant. The DeltahydABC mutant was complemented with hydABC operons modified by artificial stop codons in hydA (StopA) or at the 5'-end of hydC (StopC). The StopC mutant lacked HydC, and the hydrophobic C-terminus of HydA was missing in the hydrogenase of the StopA mutant. The two mutants catalyzed benzyl viologen reduction by H2. The enzyme activity was located in the membrane of the mutants. A mutant with both modifications (StopAC) contained the activity in the periplasm. The three mutants did not grow with H2 and either fumarate or polysulfide, and did not catalyze dimethylnaphthoquinone reduction by H2. We conclude that the same hydrogenase serves in the anaerobic respiration with fumarate and with polysulfide. HydC and the C-terminus of HydA appear to be required for both routes of electron transport and for dimethylnaphthoquinone reduction by H2. The hydrogenase is anchored in the membrane by HydC and by the C-terminus of HydA. The catalytic subunit HydB is oriented towards the periplasmic side of the membrane.

Amino Acid Sequence↗
PubMed2000

Differential uptake of fumarate by Candida utilis and Schizosaccharomyces pombe.

The dicarboxylic acid fumarate is an important intermediate in cellular processes and also serves as a precursor for the commercial production of fine chemicals such as L-malate. Yeast species differ remarkably in their ability to degrade extracellular dicarboxylic acids and to utilise them as their only source of carbon. In this study we have shown that the yeast Candida utilis effectively degraded extracellular fumarate and L-malate, but glucose or other assimilable carbon sources repressed the transport and degradation of these dicarboxylic acids. The transport of both dicarboxylic acids was shown to be strongly inducible by either fumarate or L-malate while kinetic studies suggest that the two dicarboxylic acids are transported by the same transporter protein. In contrast, Schizosaccharomyces pombe effectively degraded extracellular L-malate, but not fumarate, in the presence of glucose or other assimilable carbon sources. The Sch. pombe malate transporter was unable to transport fumarate, although fumarate inhibited the uptake of L-malate.

Biological Transport, Active↗
PubMed2000

Fumaric acid: an overlooked form of fixed carbon in Arabidopsis and other plant species.

Photoassimilates are used by plants for production of energy, as carbon skeletons and in transport of fixed carbon between different plant organs. Many studies have been devoted to characterizing the factors that regulate photoassimilate concentrations in different plant species. Most studies examining photoassimilate concentrations in C3 plants have focused on analyzing starch and soluble sugars. However, work presented here demonstrates that a number of C3 plants, including the popular model organism Arabidopsis thaliana (L.) Heynh., and agriculturally important plants, such as soybean, Glycine max (L.) Merr., contain significant quantities of fumaric acid. In fact, fumaric acid can accumulate to levels of several milligrams per gram fresh weight in Arabidopsis leaves, often exceeding those of starch and soluble sugars. Fumaric acid is a component of the tricarboxylic acid cycle and, like starch and soluble sugars, can be metabolized to yield energy and carbon skeletons for production of other compounds. Fumaric acid concentrations increase with plant age and light intensity in Arabidopsis leaves. Moreover, Arabidopsis phloem exudates contain significant quantities of fumaric acid, raising the possibility that fumaric acid may function in carbon transport.

Arabidopsis↗