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PubMed1984

Effects of succinate on amino acid incorporation into protein during chemical carcinogenesis.

The starting point of this study is the observation that succinate, the well-known Krebs cycle intermediate, strongly inhibits the incorporation of amino acids into protein of tissue slices. The results presented in this paper show that this somewhat peculiar succinate effect, which is present in regenerating liver and in a well-differentiated hepatoma and absent in two anaplastic hepatomas, is well-marked in all stages of hepatic carcinogenesis by N,N'-dimethyl-4-aminoazobenzene. A working hypothesis is that the inhibition by succinate of the amino acid incorporation into protein is mediated by a shift of the redox level in the cell toward a more reduced condition.

Amino Acids↗

PubMed2000

Facile synthesis of optically active gamma-lactones via lipase-catalyzed reaction of 4-substituted 4-hydroxybutyramides.

Lipase-catalyzed transesterification of racemic 4-substituted 4-hydroxybutyramides with succinic anhydride proceeded enantioselectively to afford (S)-succinic acid monoester and unreacted (R)-4-hydroxybutyramide derivative, which were separated easily by treatment with an alkaline solution. Both enantiomers were converted easily to optically active gamma-substituted gamma-butyrolactones.

4-Butyrolactone↗

PubMed1996

Regulation of GABA level in rat brain synaptosomes: fluxes through enzymes of the GABA shunt and effects of glutamate, calcium, and ketone bodies.

Stable isotopes were used to measure both the rate of GABA formation by glutamic acid decarboxylase (GAD) and the rate of utilization by GABA-transaminase (GABA-T). The initial rate of GABA accumulation, determined with either [2-15N]glutamine or [2H5]glutamine as precursor, was 0.3-0.4 nmol/min/mg of protein. Addition of the calcium ionophore A23187 enhanced GAD activity, whereas changes in levels of inorganic phosphate and H+ were without influence. Flux through GABA-T (GABA--> glutamate), measured with [15N]GABA as precursor, was 0.82 nmol/min/mg of protein, whereas the reamination of succinic acid semialdehyde (reverse flux through GABA-T) was almost sixfold faster, 4.8 nmol/min/mg of protein. The rate of GABA metabolism via the tricarboxylic acid cycle was very slow, with the upper limit on flux being 0.03 nmol/min/mg of protein. Addition of either acetoacetate or beta-hydroxybutyrate raised the internal content of glutamate and reduced that of aspartate; the GABA concentration and the rate of its formation increased. It is concluded that in synaptosomes (a) GABA-T is a primary factor in regulating the turnover of GABA, (b) a major regulator of GAD activity is the concentration of internal calcium, (c) GAD in nerve endings may not be saturated with its substrate, glutamate, and the concentration of the latter is a determinant of flux through this pathway, and (d) levels of ketone bodies increase, and maintain at a higher value, the synaptosomal content of GABA, a phenomenon that may contribute to the beneficial effect of a ketogenic diet in the treatment of epilepsy.

4-Aminobutyrate Transaminase↗

PubMed2005

Determination of the GABA analogue succinic semialdehyde in urine and cerebrospinal fluid by dinitrophenylhydrazine derivatization and liquid chromatography-tandem mass spectrometry: application to SSADH deficiency.

Succinic semialdehyde (SSA) accumulates in the inborn error of meta- bolism succinic semialdehyde dehydrogenase deficiency owing to impaired enzymatic conversion to succinic acid. We developed a stable-isotope dilution liquid chromato- graphy-tandem mass spectrometry method for the determination of SSA in urine and cerebrospinal fluid samples. Stable-isotope-labelled [13C4]SSA, serving as internal standard, was prepared by reaction of ninhydrin with L-[13C5]glutamic acid. SSA in body fluids was converted to its dinitrophenylhydrazine (DNPH) derivative, without sample purification prior to the derivatization procedure. The DNPH derivative of SSA was injected onto a C18 analytical column and chromatography was performed by isocratic elution. Detection was accomplished by tandem mass spectrometry operating in the negative multiple-reaction monitoring mode. The limit of detection was 10 nmol/L and the calibration curves over the range 0-500 pmol of SSA showed good linearity (r2 > 0.99). The intra-day coefficient of variation (n = 10) for urine was 2.7% and inter-day coefficient of variation (n = 5) for urine was 8.5%. The average recoveries performed on two levels by enriching urine and cerebrospinal fluid samples ranged between 85 and 115%, with coefficients of variation < 8%. The method enabled the first determination of normal values for SSA in urine and pathological values of SSA in urine and cerebrospinal fluid samples derived from patients with succinic semialdehyde dehydrogenase deficiency.

Blood Chemical Analysis↗

PubMed2001

Activity of adventitious Enterococcus strains on model curdled caprine milk: microbial growth and evolution of concentration of organic acids and lactose throughout time.

Enterococci offer a few unique advantages when compared with other lactic acid bacteria in that they are resistant to phages, stable lactose fermenters, tolerant to relatively high concentrations of sodium chloride and optimal growers at relatively high temperatures (Franz et al., 1999). Such genus occurs and grows in a variety of cheeses, especially artisanal cheeses produced in Southern Europe usually from raw milk; they are claimed to play a major role in ripening and aroma development in such cheeses (Freitas et al., 1995; Macedo et al., 1995). Enterococci can produce lactic, acetic, propionic and succinic acids (Ocando et al., 1994), compounds that have been correlated with flavor characteristics of cheese; hence strains of Enterococcus have been successfully used as starters for different cheese (Franz et al., 1999).

Animals↗

PubMed1986

Characteristics of the active oxygen in covalent binding of the pesticide methoxychlor to hepatic microsomal proteins.

This study examined the characteristics of the active oxygen species involved in generation of the reactive intermediate of methoxychlor which covalently binds to liver microsomal proteins. The possibility that the active oxygen participating in the above reaction is the superoxide anion (O2-) or a species generated from O2- was examined with the help of superoxide dismutase (SOD) and with an SOD-mimetic agent, CuDIPS [Cu2+(3,5-diisopropylsalicylic acid)2]. It was observed that, whereas CuDIPS inhibited covalent binding of methoxychlor metabolite(s), SOD did not. However, ZnDIPS [Zn2+(3,5-diisopropylsalicylic acid)2], which exhibits no SOD-mimetic activity, did not inhibit covalent binding. Furthermore, both CuDIPS and ZnDIPS had little or no effect on the formation of demethylated (polar) metabolites of methoxychlor, demonstrating that the inhibition of covalent binding by CuDIPS was not merely due to a general inhibition of the hepatic monooxygenase system. These findings suggested that O2- was involved in covalent binding, but was not accessible to SOD. Additional support for O2- involvement stems from the observation that alpha-tocopheryl acid succinate markedly inhibited covalent binding of methoxychlor. The possibility that hydrogen peroxide (H2O2) was involved in covalent binding of methoxychlor appears unlikely. Catalase had no effect on covalent binding when NADPH was the cofactor, and the use of H2O2 in place of NADPH did not yield covalent binding. Certain scavengers of hydroxyl radical (ethanol, t-butanol and benzoate) inhibited, and other known scavengers (DMSO and mannitol) did not inhibit, covalent binding. EDTA stimulated binding, desferal (desferrioxamine) exhibited no effect on binding, and diethylenetriaminepentaacetic acid (DETAPAC) inhibited binding. A possible explanation for this observation is that the Fe2+ needed for generation of X OH is much more easily obtained from Fe3+-EDTA than from Fe3+-desferal, which resists reduction. The inhibitory effect by DETAPAC may be due to chelation of another metal which is needed for the reaction. Lastly, certain scavengers of singlet oxygen inhibited covalent binding with little effect on the formation of polar metabolites of methoxychlor. In conclusion, these studies support the involvement of X OH and singlet oxygen, possibly derived from O2-, in the formation of the reactive methoxychlor intermediate.(ABSTRACT TRUNCATED AT 400 WORDS)

Benzoates↗

PubMed1969

Role of glycols and tweens in the production of ergot alkaloids by Claviceps paspali.

Several glycols and Tweens markedly stimulated the production of ergot alkaloids in submerged cultures of Claviceps paspali. The role of these compounds was investigated in shake flasks and bench-scale fermentors. 2,3-Butanediol was not utilized by the fungus, and 1,2-propanediol-1-(14)C was not incorporated into the alkaloids. Glycols and Tweens lowered the surface tension of the basal medium and promoted the utilization of metabolites. In the presence of glycols and Tweens, an increased uptake of labeled sorbitol and succinic acid took place, whereas the specific radioactivity of the alkaloids was not affected. These results indicated that glycols and Tweens are not involved directly in the biosynthetic process; they apparently acted as surface-active agents, facilitating transport of metabolites into the cells.

Ascomycota↗

PubMed2000

Neuroprotection produced by the NAALADase inhibitor 2-PMPA in rat cerebellar neurons.

The present study examined the neuroprotective actions of the N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) inhibitor 2-(phosphonomethyl)pentanedioic acid (2-PMPA) in four in vitro models of neurotoxicity. Using neuron-enriched primary cultures derived from rat embryo (E15) cerebellum, 2-PMPA afforded 100% neuroprotection from injuries induced by hypoxia (EC(50)=8.4 microM). In contrast, against glutamate or N-methyl-D-aspartate (NMDA) injury, 2-PMPA was less potent and its efficacy limited to a maximum of 46% and 16%, respectively. 2-PMPA was not effective against veratridine-induced injury. Also, the less potent analog of 2-PMPA, 2-[phosphonomethyl]succinic acid (2-PMSA), was ineffective. Unlike 2-PMPA, the endogenous NAALADase substrate and mGlu(3) receptor agonist N-acetyl-aspartyl-glutamate (NAAG) was neuroprotective against all four injury mechanisms and compared to 2-PMPA, exhibited a different "phosphate effect" on neuroprotection. These results confirm the superior efficacy of 2-PMPA to protect against injury caused by cellular anoxia, and are discussed relative to upstream modulation of hyperglutamatergic activity vs. downstream modulation of metabotropic receptors as possible targets for ischemia/stroke therapy.

Animals↗

PubMed1965

The metabolism of beta-phenylpropionic acid by an Achromobacter.

1. When a species of Achromobacter grew with beta-phenylpropionate as carbon source, 2-hydroxy-beta-phenylpropionate and 2,3-dihydroxy-beta-phenylpropionate appeared in the growth medium. The concentrations of these compounds were maximal during exponential growth. 2. The cells contained an oxygenase that required Fe(2+) ions and cleaved the benzene nucleus between the adjacent carbon atoms that bear the side chain and one hydroxyl group of 2,3-dihydroxy-beta-phenylpropionate. 3. The ring-fission product, formed with the consumption of 1mol. of oxygen/mol. of substrate, was isolated and a chemical structure assigned. Sephadex-treated cell extracts converted 1mol. of this compound into 1mol. of 4-hydroxy-2-oxovalerate without oxygen consumption; succinic acid was also formed. 4. When Mn(2+) ions or Mg(2+) ions were added, dialysed extracts converted 4-hydroxy-2-oxovalerate into pyruvate and acetaldehyde, but the reaction did not proceed to completion.

Alcaligenes↗

PubMed2004

Fermentative production of chemicals that can be used for polymer synthesis.

The fermentative production of chemicals that can be used as monomers for the synthesis of polymers has become an important topic in biotechnology research because of the limited nature of petroleum and environmental issues. In particular, the fermentative production of metabolites such as dicarboxylic acids, amino acids, and diols, which are suitable as building blocks for subsequent polymerization, has attracted much attention. Various wild-type and metabolically engineered microorganisms have been developed for the efficient production of these chemicals from renewable resources. In addition, the development of fermentation strategies to achieve the highest possible productivities has been another focus of research, considering that these monomers should be produced at costs low enough to compete with petroleum-derived ones. In this paper, the metabolic pathways leading to the synthesis of such important monomers including succinic acid, lactic acid, fumaric acid, propan-1,2-diol, and propan-1,3-diol are reviewed. In addition, the metabolic engineering and fermentation strategies for their production are reviewed.

Biotechnology↗

PubMed1997

Unusual mechanism of oxygen atom transfer and product rearrangement in the catalytic reaction of 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase.

The oxygenation reaction of 2-methyl-3-hydroxypyridine-5-carboxylic acid (MHPC) oxygenase with the substrate, MHPC, was investigated. Two oxygenated flavin intermediates C(4a)-hydroperoxy flavin and C(4a)-hydroxy flavin were found, implying that the enzyme functions similarly to flavoprotein hydroxylases. This finding is supported by the results of independent oxygen-18 tracer experiments, which showed that one atom of oxygen from 18O2 and one atom of oxygen from H218O are incorporated in the product. MHPC oxygenase normally catalyzes both the oxygenation and the hydrolytic ring opening of the pyridine ring of MHPC to yield the acyclic compound, alpha-(N-acetylaminomethylene)succinic acid. Using 5-hydroxynicotinic acid (5HN), which has no 2-methyl group, we tested whether the hydrolytic reaction was due to the presence of the 2-methyl group on MHPC (that prevented rearomatization of the initial product) or to the specific properties of MHPC oxygenase. Product analysis of the enzymatic reaction of 5HN and MHPC oxygenase shows that the enzyme catalyzes the hydroxylation and subsequent hydrolysis of the hydroxylated substrate to yield an acyclic product. The investigation of the oxygenation reaction demonstrates that the enzyme uses the same mechanism to catalyze the 5HN reaction as it does in the MHPC reaction.

Azides↗

PubMedDate not supplied

[Changes in oxidative phosphorylation following exposure to sodium caffeine benzoate].

Sodium caffeine-benzoate at concentrations 6 x 10(-6) M and 6 x 10(-5) M increased the rate of free oxidation of succinic acid in myocardial mitochondria suggesting possibility of uncoupling of respiration and oxidative phosphorylation. The drug stimulates the free flow of electrons in respiratory chain. These phenomena might be responsible for an increase in metabolism and body temperature in patients after the treatment with this drug.

Animals↗

PubMed1979

Biochemical characterization of unidentified microaerophilic cocci isolated from heifer and dry-cow mastitis.

Thirty-nine strains of gram-positive microaerophilic cocci isolated from cases of heifer and dry-cow mastitis were biochemically characterized with the API 50E and API-ZYM test kit systems, gas-liquid chromatography for analysis of end products of glucose metabolism, and anaerobic biochemical tests (L. V. Holdeman, E. P. Cato, and W. E. C. Moore, Anaerobe Laboratory Manual, Virginia Polytechnic Institute, Blacksburg, 1977). Strains were screened for production of a variety of extracellular enzymes on substrate-containing agar plates and for hemolysin and coagulase production. Antibiotic susceptibility and sensitivity tests were also performed. The microaerophilic cocci displayed homogeneity with respect to the majority of the biochemical tests used; i.e., greater than or equal to 90% of the strains were consistently positive or negative in any one test and probably represent one species. All produced deoxyribonuclease, ribonuclease, and hyaluronidase, and 92% were positive for chondroitin sulfatase. Catalase and coagulase tests were negative. Greening was observed on bovine blood agar. Acetic and succinic acids were produced by all strains as the only detectable products of glucose metabolism. The strains were susceptible to penicillin G, cefoxitin, doxycycline, and chloramphenicol and were resistant to clindamycin, novobiocin, and metronidazole. Their taxonomic position remains unclear.

Acetates↗

PubMed2000

Routine analysis of short-chain fatty acids for anaerobic bacteria identification using capillary electrophoresis and indirect ultraviolet detection.

The diagnosis of anaerobes can be difficult to perform, using classical biochemical tests. Characterization of metabolic end-products such as short-chain fatty acids (SCFA) was often used because of their reproducible biosynthesis. Despite this, SCFA are difficult to study using gas chromatography, due to their high volatility. Furthermore, the treatment of the samples are long and fastidious. Capillary electrophoresis and indirect UV detection (CE-indirect UV) is a well-known analytical method to study inorganic or organic anions. In this work, we validate the analysis of SCFA using CE-indirect UV detection. To do this, we studied the culture media of 98 anaerobic strains for the detection and quantitation of the following acids: succinic, pyruvic, acetic, lactic, propionic, 2-hydroxybutyric, butyric, 2-hydroxyvaleric, isovaleric, isocaproic, and 3-phenylpropionic. We verified that the CE-indirect UV detection analysis of SCFA for taxonomical data can be used as a mean for rapid identification for the study of anaerobes.

Bacteria, Anaerobic↗

PubMed2002

Hybrid dendritic-linear polyester-ethers for in situ photopolymerization.

Novel first through fourth generation hybrid dendritic-linear copolymers, composed entirely of building blocks known to be biocompatible or degradable to natural metabolites in vivo, are described. Specifically, these copolymers are composed of poly(ethylene glycol), glycerol, and succinic acid and are synthesized using a divergent approach in high yield. A photo-cross-linkable derivative of this copolymer successfully seals 4.1 mm corneal lacerations. The mechanism of tissue repair is likely one of physical entrapment where an interpenetrating network (IPN) is formed between the cross-linked copolymer and the tissue.

Eye Injuries↗

PubMed2005

Enhanced adsorption of Cd (II) on a hydrous Al (III) floc in the presence of a modified form of polyethylenimine.

A polymer modified with succinic anhydride has been investigated for the adsorption of cadmium (II) on a freshly precipitated aluminium (III) hydroxide floc. The proportion of chelate attached to the polymer is varied to determine the relationship between carboxyl and amino groups on the polyelectrolyte, in terms of enhanced adsorption of cadmium (II) on a hydrous aluminium floc. The presence of polyelectrolyte enhanced the adsorption of 3.3 ppm Cd (II) on a 333 ppm Al (III) floc at every concentration of polyelectrolyte investigated. The proportion of succinic anhydride attached to the polymer had an impact on the increased adsorption of Cd (II) on an Al (III) floc observed. A decreasing proportion of succinic anhydride to polymer resulted in a decrease in the amount of cadmium adsorbed on the floc. Above pH 8, a decrease in the % Cd (II) adsorbed on the floc and % Al (III) retained within the floc decreases with the presence of polyelectrolyte as a result of the formation of soluble Cd-Polyethylenimine-succinic acid (PEISA) complexes. When the Al-PEISA combination was applied to a complex matrix where Cd (II), Cu (II) and Ni (II) ions competed for adsorption, enhanced adsorption was observed for Cd (II) and Ni (II). At pH 7, dissolution of the floc observed with the addition of discrete chelates was not observed with the addition of polyelectrolytes.

Adsorption↗

PubMed1999

Repaglinide, a new oral antidiabetic agent: a review of recent preclinical studies.

Repaglinide is a new carbamoylmethyl benzoic acid derivative that is structurally related to meglitinide. In common with all active oral hypoglycaemic agents, it displays a comparable U-shaped configuration. Repaglinide exerts its effects by binding to a site on the plasma membrane of beta-cells, thereby closing ATP-sensitive potassium channels. This causes depolarization of the beta-cell and the opening of voltage-sensitive calcium channels allowing the influx of extracellular calcium ions. This increase in intracellular calcium, in turn, stimulates insulin release. The insulinotropic effect of repaglinide is not related to its ionophoretic capacity. Repaglinide does not cause insulin release in the absence of exogenous glucose, nor does it inhibit the biosynthesis of proinsulin. In vivo administration of an ester of succinic acid potentiates the insulin secretory response to concomitantly administered repaglinide. Repaglinide causes a more rapid increase in plasma insulin levels in rats than either glibenclamide or glimepiride.

Administration, Oral↗

PubMed1994

Impaired in vivo insulin secretion in response to non-glucidic secretagogues in adult rats after neonatal streptozotocin.

In the perfused pancreas of adult rats that were injected with streptozotocin (STZ) during the neonatal period, the release of insulin caused by glucose is more severely affected than that evoked by other secretagogues. We have now examined whether a comparable situation prevails in vivo. In anesthetised rats, the 0-10 min plasma insulin incremental area recorded after intravenous glucose administration (2.8 mumol/g body wt) was severely decreased in STZ rats, with a K value for glucose utilization of 1.9 +/- 0.2 x 10(-2)/min, as compared with control rats, with a K value of 4.4 +/- 0.4 x 10(-2)/min. At the 2nd min of the test, the plasma insulin increment was about 5 times lower in STZ than control rats. After glibenclamide administration (0.1 nmol/g body wt), the insulin incremental area was 3 times lower in STZ than control rats. Relative to the post-prandial readings, the plasma glucose concentration was decreased to the same extent, however, in control and STZ rats injected with glibenclamide. The secretory response to succinic acid methyl ester (SAM; 1.0 mumol/g body wt) was virtually abolished in the STZ rats. In the latter animals, SAM also failed to enhance the hypoglycemic action of glibenclamide in contrast to the situation found in control rats. Iterative intraperitoneal administration of SAM (1.0 mumol/g body wt) thrice daily for 7-10 days failed to improve significantly the insulin secretory response to glucose or glibenclamide, whether in control or STZ rats. These findings indicate that the altered metabolism of glucose in the B cell of STZ rats coincides with an impaired secretory response to glibenclamide and SAM, as possibly attributable, in part at least, to a loss of the modulating action of glucose upon the secretory response to the hypoglycemic sulfonylurea and succinate ester.

Animals↗