Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MALONATES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2000

Identification and characterization of a novel transcriptional regulator, MatR, for malonate metabolism in Rhizobium leguminosarum bv. trifolii.

A novel gene, matR, located upstream of matABC, transcribed in the opposite direction, and encoding a putative regulatory protein by sequence analysis was discovered from Rhizobium leguminosarum bv. trifolii. The matA, matB, and matC genes encode malonyl-CoA decarboxylase, malonyl-CoA synthetase, and a presumed malonate transporter, respectively. Together, these enzymes catalyze the uptake and conversion of malonate to acetyl-CoA. The deduced amino-acid sequence of matR showed sequence similarity with GntR from Bacillus subtilis in the N-terminal region encoding a helix-turn-helix domain. Electrophoretic mobility shift assay indicated that MatR bound to a fragment of DNA corresponding to the mat promoter region. The addition of malonate or methylmalonate increased the association of MatR and DNA fragment. DNase I footprinting assays identified a MatR binding site encompassing 66 nucleotides near the mat promoter. The mat operator region included an inverted repeat (TCTTGTA/TACACGA) centered -46.5 relative to the transcription start site. Transcriptional assays, using the luciferase gene, revealed that MatR represses transcription from the mat promoter and malonate alleviates MatR-mediated repression effect on the expression of Pmat-luc+ reporter fusion.

Amino Acid Sequence↗
PubMed1996

Neuronal loss and cytoskeletal disruption following intrahippocampal administration of the metabolic inhibitor malonate: lack of protection by MK-801.

Impaired energy metabolism may contribute to the pathogenesis of late-onset neurodegenerative disorders such as Alzheimer's disease by increasing neuronal vulnerability to excitotoxic damage through the NMDA receptor. The effects of metabolic impairment on the striatum have been extensively examined, but relatively little is known regarding the vulnerability of the hippocampus. To examine the effect of metabolic impairment on the hippocampal formation, malonate (0.25-2.5 mumol), a reversible inhibitor of succinate dehydrogenase, was administered by stereotaxic injection into the hippocampus of male Sprague-Dawley rats. Neuronal loss was assessed by Nissl stain, and immunocytochemistry was used to examine cytoskeletal disruption. Malonate produced a dose-dependent lesion in which CA1 pyramidal neurons were most vulnerable, followed by CA3 and dentate gyrus. Cytoskeletal alterations included the loss of microtubule-associated protein 2 (MAP2) and dendritic MAP1B immunoreactivity, whereas axonal MAP1B and tau proteins were relatively spared. Spatially and temporally correlated with the loss of MAP2 was an increase in the immunoreactivity of calpain-cleaved spectrin. A similar pattern of neuronal damage and cytoskeletal disruption was produced by intrahippocampal injection of quinolinate (0.1 mumol), an NMDA agonist. Although these results are consistent with the hypothesis that metabolic impairment results in excitotoxic death, MK-801 (dizocilipine maleate), a noncompetitive NMDA receptor antagonist, did not attenuate the lesions produced by malonate but was effective against quinolinate. The results suggest that NMDA receptor activation is not required for malonate-induced damage in the hippocampal formation.

Animals↗
PubMed2000

Malonate and 3-nitropropionic acid neurotoxicity are reduced in transgenic mice expressing a caspase-1 dominant-negative mutant.

Increasing evidence implicates caspase-1-mediated cell death as a major mechanism of neuronal death in neurodegenerative diseases. In the present study we investigated the role of caspase-1 in neurotoxic experimental animal models of Huntington's disease (HD) by examining whether transgenic mice expressing a caspase-1 dominant-negative mutant are resistant to malonate and 3-nitropropionic acid (3-NP) neurotoxicity. Intrastriatal injection of malonate resulted in significantly smaller striatal lesions in mutant caspase-1 mice than those observed in littermate control mice. Caspase-1 was significantly activated following malonate intrastriatal administration in control mice but significantly attenuated in mutant caspase-1 mice. Systemic 3-NP treatment induced selective striatal lesions that were significantly smaller within mutant caspase-1 mice than in littermate control mice. These results provide further evidence of a functional role for caspase-1 in both malonate- and 3-NP-mediated neurotoxin models of HD.

Animals↗
PubMed2003

Effects of cannabinoids in the rat model of Huntington's disease generated by an intrastriatal injection of malonate.

Cannabinoids could provide neuroprotection in neurodegenerative disorders. In this study, we examined whether a treatment with Delta9-tetrahydrocannabinol, a non-selective cannabinoid receptor agonist, or with SR141716, a selective antagonist for the cannabinoid CB(1) receptor subtype, could affect the toxicity of the complex II reversible inhibitor malonate injected into the striatum, which replicates the mitochondrial complex II deficiency seen in Huntington's disease patients. As expected, malonate injection produced a significant reduction in cytochrome oxidase activity in the striatum consistent with the expected neurodegeneration caused by this toxin. The administration of Delta9-tetrahydrocannabinol increased malonate-induced striatal lesions compared to vehicle and, surprisingly, SR141716, far from producing effects opposite to those of Delta9-tetrahydrocannabinol, also enhanced malonate effects, and to an even greater extent. In summary, our results are compatible with the idea that manipulating the endocannabinoid system can modify neurodegeneration in Huntington's disease, and suggest that highly selective CB(1) receptor agonists might be necessary to produce neuroprotective effects against indirect excitotoxicity.

Animals↗
PubMed2004

Valproate is neuroprotective against malonate toxicity in rat striatum: an association with augmentation of high-affinity glutamate uptake.

The antiepileptic drug valproate (VPA) may be neuroprotective. We treated rats with VPA for 14 days (300 mg/kg twice daily) before intrastriatal injection of 1.5 micromol (1 M) of the succinate dehydrogenase inhibitor malonate. VPA-treated animals developed smaller lesions than control animals: 10 +/- 2 mm(3) versus 26 +/- 8 mm(3) (means +/- SD; P = 10(-4). Injection of NaCl that was equiosmolar with 1 M malonate caused lesions of only 1.2 +/- 0.4 mm(3) in control animals, whereas physiologic saline produced no lesion. VPA pretreatment reduced the malonate-induced extracellular accumulation of glutamate. This effect paralleled an increase in the striatal level of the glutamate transporter GLT, which augmented high-affinity glutamate uptake by 25%, as determined from the uptake of [(3)H] glutamate into striatal proteoliposomes. Malonate caused a 76% reduction in striatal adenosine triphosphate (ATP) content, but the glial, ATP-dependent formation of glutamine from radiolabeled glucose or glutamate was intact, indicating that glial ATP production supported uptake of glutamate. Striatal levels of HSP-70 and fos were reduced, and the levels of bcl-2 and phosphorylated extracellular signal-regulated kinase remained unaffected, but histone acetylation was increased by VPA treatment. The results suggest that augmentation of glutamate uptake may contribute importantly to VPA-mediated neuroprotection in striatum.

Adenosine Triphosphate↗
PubMed1989

Effects of malonate administration on renal ammoniagenesis in intact dogs.

In the dog kidney in vivo, malonate augmented ammoniagenesis from both amide and nonamide nitrogen sources, similar to previous in vitro investigations using incubating canine renal tubules. This was highly significant in alkalotic dogs, where it was accompanied by decreased renal tissue concentrations of glutamate. Changes in renal ammonia metabolism were less evident in acidotic dogs where a markedly decreased glomerular filtration rate was noted following malonate administration. Under conditions of complete ureteric obstruction which effectively abolished glomerular filtration, malonate significantly augmented ammoniagenesis above baseline in acidotic dogs. These in vivo results with malonate have similarities to those seen in dogs subjected to an acid challenge alone and suggest that the adaptation in renal ammoniagenesis under both circumstances occurs via enhanced deamination of glutamate pools.

Acidosis↗
PubMed2002

Malonate metabolism: biochemistry, molecular biology, physiology, and industrial application.

Malonate is a three-carbon dicarboxylic acid. It is well known as a competitive inhibitor of succinate dehydrogenase. It occurs naturally in biological systems, such as legumes and developing rat brains, which indicates that it may play an important role in symbiotic nitrogen metabolism and brain development. Recently, enzymes that are related to malonate metabolism were discovered and characterized. The genes that encode the enzymes were isolated, and the regulation of their expression was also studied. The mutant bacteria, in which the malonate-metabolizing gene was deleted, lost its primary function, symbiosis, between Rhizobium leguminosarium bv trifolii and clover. This suggests that malonate metabolism is essential in symbiotic nitrogen metabolism, at least in clover nodules. In addition to these, the genes matB and matC have been successfully used for generation of the industrial strain of Streptomyces for the production of antibiotics.

Amidohydrolases↗
PubMedDate not supplied

Determination of the thermodynamic parameters and stability constants of UO2(2+), Th4+, and Ce3+ complexes with some azo-benzene-N-malonic acid derivatives.

Proton-ligand dissociation and metal-ligand formation constants of azobenzene-N-malonic acid (I), p-Cl-azobenzene-N-malonic acid (II), p-Br-azobenzene-N-malonic acid (III) and p-COOH- azobenzene-N-malonic acid (IV) with UO2(2+), Th4+ and Ce3+ were evaluated potentiometrically using Bjerrum's method at 25, 35 and 45 +/- 0.5 degrees C and ionic strength 0.1 M in 40% v/v ethanol-water medium. The order of stability constants was found to be Ce3+ > Th4+ > UO2(2+). The effect of temperature on the dissociation and stability constants of the formed complexes was studied and the corresponding thermodynamic functions were derived and discussed. The ratio of metal-ligand was determined conductometrically. The structure of the ligands under investigation as well as their metal complexes has been elucidated by elemental analysis, IR and 1HNMR spectroscopy.

Azo Compounds↗
PubMed1985

Effects of malonic, maleic, citric and caffeic acids on the motility of human sperm and penetration of cervical mucus.

The spermicidal effect of four organic acids (malonic, maleic, citric and caffeic acids) was evaluated by adding the acids to sperm, and by observing sperm survival and penetration following addition of these acids to human cervical mucus. Direct addition of 0.1% malonic, maleic and citric acid rendered the sperm immotile by a reduction of pH. In capillaries filled with cervical mucus, the incorporation of 0.01% maleic, malonic and citric acids was sufficient to reduce sperm penetration, and at 0.1%, penetration was completely abolished. Thus, malonic, and maleic and citric acids show promise as cervical or vaginal contraceptives. Caffeic acid was found to be unsuitable owing to its insolubility in aqueous media. Electron microscopy indicated that human sperm do not undergo the acrosome reaction while penetrating cervical mucus in vitro.

Caffeic Acids↗
PubMedDate not supplied

[Pathways of endogenous malonate formation in the rat liver].

Malonic acid is one of the intermediates of cell metabolism. Malonic dialdehyde and malonyl coenzyme A may be important precursors of malonate. The correlation of biosynthesis intensity and utilization of malonate determines capacity of its intracellular pool. It is supposed that pool capacity is related both to metabolism regulation and to functional condition of organs and tissues.

Animals↗
PubMed1993

[The effect of malonic acid on the rate of fibroblast proliferation in culture].

The influence of malonic acid on the proliferation rate of cultured human fetal [correction of embryo] skin fibroblasts was investigated. Addition of malonate to the serum-less incubation mixture stimulated fibroblast proliferation. The maximum stimulation occurred in the medium at the 0.01 mM concentration of malonic acid. When the cells were cultured in the medium with serum, the influence of malonate on the cells proliferation increased.

Cells, Cultured↗
PubMed2002

A highly regioselective approach to multiple adducts of C60 governed by strain minimization of macrocyclic malonate addends.

New macrocyclic malonates 2-5 have been prepared by reaction of malonyl dichloride with alkanediols. Reactions of these cyclo-[n]-alkylmalonates with C60 are highly regioselective. The macrocycles containing identical alkyl spacers selectively form bis- and trisadducts of C60 with rotational symmetry. The addition pattern of the regioselectively formed oligoadducts is determined by the size of the alkyl spacer within the macrocyclic malonate. A variety of bis-, tris-, tetra-, and hexaadducts have been synthesized to show the scope of this approach. "Exotic" addition patterns such as trans-4,trans-4,trans-4, which has been synthesized and completely characterized for the first time, are also accessible by this method. The regioselectivity is ruled by the even distribution of the strain within the macrocyclic malonates containing spacer alkane chains of identical lengths: addition patterns with rotational symmetry provide exactly identical distances of the malonate oxygen atoms and are thus exclusively formed by this method. In contrast, when macrocycles with two different alkyl spacer lengths are used, such as 9 and 10, the reaction exclusively yields C(s)-symmetric bisadducts.

Journal Article↗
PubMed2005

Use of Malone antegrade continence enema in patients with perineal colostomy after rectal resection.

PURPOSE: Abdominoperineal resection, with iliac colostomy, remains the gold standard treatment for very low-lying rectal cancer, but it alters patients' quality of life. Alternatives to iliac colostomy need to be experimented. Antegrade enemas via a cecal access (Malone operation) obtains a colonic emptying and improves continence for incontinent patients. Continence and quality of life after abdominoperineal resection and perineal colostomy associated to a Malone antegrade continence enema were studied. METHODS: After abdominoperineal resection for cancer, 18 patients had a digestive reconstruction by perineal colostomy and Malone antegrade continence enema. Patients performed antegrade enemas every 24 to 48 hours with tap water. After six months, continence (Cleveland Clinic score) and quality of life (Fecal Incontinence Quality of Life scale) were recorded. RESULTS: Morbidity was 5 percent (1 appendix necrosis). All patients could perform antegrade enemas by themselves. Mean continence score was 6.41/20 (standard error, 2.31). Fecal Incontinence Quality of Life scores were: lifestyle 3.18/4 (standard error, 0.83); coping/ behavior 2.99/4 (standard error, 0.83); depression/self-perception 3.11/4 (standard error, 0.83); embarrassment 2.84/4 (standard error, 0.63). CONCLUSIONS: After abdominoperineal resection, Malone antegrade continence enema associated to perineal colostomy provided an acceptable continence. It preserved patients' body image and resulted in a satisfying quality of life. It could become an alternative to iliac colostomy in selected patients.

Adult↗
PubMed2005

An ATR-FTIR spectroscopic study of the competitive adsorption between oxalate and malonate at the water-goethite interface.

The competitive adsorption between oxalate and malonate at the water-goethite interface was studied as a function of pH and total ligand concentrations by means of quantitative adsorption measurements and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. The results obtained show that ATR-FTIR spectroscopy resolves the individual spectroscopic features of oxalate and malonate when adsorbed simultaneously at the water-goethite interface. The characteristic peaks of all four types of predominating surface complexes existing in the single ligand systems were identified, namely one inner sphere and one outer sphere surface complex for each ligand. The quantitative adsorption data showed that oxalate partially out-competes malonate at the water-goethite interface. Evaluation of the peak area variations as a function of pH indicated that the stronger oxalate adsorption can be ascribed to the more stable inner sphere surface complex of oxalate, which in turn is related to the oxalate five-member chelate ring structure yielding a more stable complex compared to the six-member ring of malonate.

Journal Article↗
PubMed1998

The Malone (antegrade colonic enema) procedure: early experience.

PURPOSE: The aim of this study was to assess the results of the Malone (antegrade colonic enema) procedure for fecal incontinence. METHODS: By a retrospective review of patients treated between 1990 and 1996 in a tertiary referral center, 36 patients were treated with a Malone procedure. Age at operation was 8.3 (range, 3 to 14) years, the mean period of follow-up was 39 (range, 9 to 72) months. The indication was fecal soiling in 35 and chronic constipation in one. The underlying diagnosis was an anorectal anomaly in the majority of patients. The appendix was used in 30 patients and a cecal flap in six, and a submucosal antireflux procedure was also performed in 10. In 35 patients, a circular stoma was created and in one a V flap was used. Antegrade colonic enemas were performed daily in 10, alternate days in 23, and in three patients the stoma was no longer used. Enemas were performed with a 10F catheter using a mixture of phosphate enema (or liquorice) and saline. RESULTS: Fecal soiling was completely controlled in 28 patients, and eight children soiled more than once a week. Complications occurred in 15 patients; the main problem was stenosis of the conduit, which occurred in 9 of 30 appendiceal stomas and three of six cecal stomas. Stomal stenosis was treated with surgical revision in eight patients. Additional complications were reflux through the stoma (n=2), pain on catheterisation (n=1), and small bowel obstruction (n=1). In one patient the Malone has been converted to a colostomy. CONCLUSIONS: The Malone procedure is a simple technique that can effectively control fecal incontinence in the majority of cases. It appeared to be better in older children. Stomal stenosis is a frequently encountered problem that may require surgical revision.

Appendix↗
PubMed1984

Indirect inactivation of rabbit reticulocyte initiation factor eIF-2 by helenalin and bis(helenalinyl) malonate.

Helenalin and bis(helenalinyl) malonate, sesquiterpene lactones that react primarily with exposed sulfhydryl groups, were shown to be equally effective inhibitors of endogenous protein synthesis in rabbit reticulocyte lysates. By use of partially fractionated systems, it was possible to show that helenalin preferentially inhibited the conversion of the ternary initiation complex to the 48S preinitiation complex. Previous experiments have shown that this preferential inhibition is due to selective inactivation of eIF-3 [Williams, W. L., Chaney, S. G., Willingham, W., Considine, R. T., Hall, I. H., & Lee, K.-H. (1983) Biochim. Biophys. Acta 740, 152-162]. Bis(helenalinyl) malonate was much less active as an inhibitor of 48S complex formation than helenalin and clearly did not possess sufficient activity in that assay to explain its effectiveness as a protein synthesis inhibitor in whole lysates. Kinetic studies also showed a clear difference between the mechanism of action of these two drugs. Bis(helenalinyl) malonate inactivated protein synthesis in reticulocyte lysates only after a lag of 10 min, and the inhibition of protein synthesis could be completely reversed by the addition of 5 mM cAMP. Helenalin showed more complex kinetics. While full inhibition only occurred after a lag of 10-15 min, a partial inhibition was observed from very early times. cAMP at 5 mM was only partially able to reverse inhibition by helenalin. Phosphorylation studies showed that both helenalin and bis(helenalinyl) malonate were equally effective at activating eIF-2 alpha kinase and indirectly causing phosphorylation of eIF-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

The acyl carrier protein of malonate decarboxylase of Malonomonas rubra contains 2'-(5"-phosphoribosyl)-3'-dephosphocoenzyme A as a prosthetic group.

Malonate decarboxylase of Malonomonas rubra is composed of soluble and membrane-bound components and contains an acetyl residue that is essential for catalytic activity. Upon incubation with hydroxylamine, the acetyl residue is removed, forming an inactive thiol enzyme, which is reactivated by acetylation with ATP, acetate, and a specific ligase. After incubation of the thiol enzyme with iodoacetate in the presence of excess dithioerythritol, the prosthetic group thiol residue was carboxymethylated and reactivation by acetylation was impaired. Radioactive labeling with [1-14C] iodoacetate revealed the site of carboxymethyation on a distinct cytoplasmic protein with the apparent molecular mass of 14 000 Da. The same protein was specifically labeled by enzymic acetylation of the thiol enzyme with [1-14C]acetate and ATP. Malonate decarboxlyation by [14C]acetyl malonate decarboxlyation resulted in the release of the radioactive acetyl residue from the enzyme,indicating that this acetyl residue is exchanged for a malonyl residue during catalysis. The acyl carrier protein has been purified as its [14C]carboxymethylated derivative to apparent homogeneity. The prosthetic group of the acyl carrier protein was isolated after alkaline hydrolysis, and its chemical structure was identified by high-performance liquid chromatography (HPLC) with the corresponding compound from citrate lyase from Klebsiella pneumoniae as reference and by mass spectrometry. Malonate decarboxylase was found to carry the same prosthetic group as citrate lyase, i.e. 2'-(5"-phosphoribosyl)-3'-dephospho-CoA.

Acyl Carrier Protein↗
PubMed2003

Ferromagnetic coupling in the three-dimensional malonato-bridged gadoliniumIII complex [Gd2(mal)3(H2O)6] (H2mal = malonic acid).

The novel gadolinium(III) complex of formula [Gd(2)(mal)(3)(H(2)O)(6)] (1) (H(2)mal = 1,3-propanedioic acid) has been prepared and characterized by X-ray diffraction analysis. Crystal data for 1: monoclinic, space group I2/a, a = 11.1064(10) A, b = 12.2524(10) A, c =13.6098(2) A, beta = 92.925(10) degrees, U = 1849.5(3) A(3), Z = 4. Compound 1 is a three-dimensional network made up of malonate-bridged gadolinium(III) ions where the malonate exhibits two bridging modes, eta(5)-bidentate + unidentate and eta(3):eta(3) + bis(unidentate). The gadolinium atom is nine-coordinate with three water molecules and six malonate oxygen atoms from three malonate ligands forming a distorted monocapped square antiprism. The shortest metal-metal separations are 4.2763(3) A [through the oxo-carboxylate bridge] and 6.541(3) A [through the carboxylate in the anti-syn coordination mode]. The value of the angle at the oxo-carboxylate atom is 116.8(2) degrees. Variable-temperature magnetic susceptibility measurements reveal the occurrence of a significant ferromagnetic interaction through the oxo-carboxylate pathway (J = +0.048(1) cm(-1), H = -JS(Gd(1)) x S(Gd(1a))).

Journal Article↗