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Direction specific interactions of 1,4-dicarboxylic acid with calcite surfaces.

Interactions of succinic acid (SUC) with the {104} cleavage faces of calcite show a strong preference in crystallographic directions. In situ atomic force microscopy revealed that the morphology of etch pits on the crystal surfaces experienced a transition from the common rhombus to a hexagon upon the introduction of SUC. The pit shape further evolved from 6-sided to 7-sided and eventually to 5-sided with increasing concentrations of SUC. Analysis indicates that the morphology changes may result from SUC preferentially binding to the [42] and [010] edges of the (104) plane to selectively slow down their step speed.

Calcium Carbonate↗

GABA, gamma-hydroxybutyric acid, and neurological disease.

gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABA is converted from glutamic acid by the action of glutamic acid decarboxylase (GAD) of which two isoforms exist GAD65 and GAD67. GABA then is broken down, both within the cell and in the synaptic cleft by GABA transaminase to form succinic semialdehyde. In turn, succinic semialdehyde is converted either to succinic acid by succinic semialdehyde dehydrogenase or into gamma-hydroxybutyric acid (GHB) by succinic semialdehyde reductase. Because GABA modulates the majority of inhibition that is ongoing in the brain, perturbations in GABAergic inhibition have the potential to result in seizures. Therefore, the most common disorder in which GABA is targeted as a treatment is epilepsy. However, other disorders such as psychiatric disease, spasticity, and stiff-person syndrome all have been related to disorders of GABAergic function in the brain. This review covers the roles of GABAergic neurotransmission in epilepsy, anxiety disorders, schizophrenia, stiff-person syndrome, and premenstrual dysphoric disorder. In the final section of this review, the GABA metabolite GHB is discussed in terms of its physiological significance and its role in epilepsy, sleep disorders, drug and alcohol addiction, and an inborn error of GABA metabolism, succinic semialdehyde dehydrogenase deficiency.

Aldehyde Oxidoreductases↗

[Mechanism of the reaction of substrate phosphorylation in the tricarboxylic acid cycle].

The suggested sequence of the reactions differs from those presented in literature and includes the following compounds as intermediate ones: the complex of enzyme having 2ATP and two residues of phosphoric acid; the complex of enzyme having four residues of phosphoric acid; the complex of enzyme containing two residues of phosphoric acid and two residues of succinic acid. Sequences of the reactions suggested in literature involve as intermediate compounds a phosphorylated derivative of the enzyme (E--P), phosphorylated derivative CoA linked with the enzyme (E.CoA--P), a high-ergic compound of the enzyme with CoA (E.CoA) and succinyl phosphate linked with the enzyme (E.succinyl--P).

Adenosine Triphosphate↗

Production of multifunctional organic acids from renewable resources.

Recently, the microbial production of multifunctional organic acid has received interest due to their increased use in the food industry and their potential as raw materials for the manufacture of biodegradable polymers. Certain species of microorganisms produce significant quantities of organic acids in high yields under specific cultivation conditions from biomass-derived carbohydrates. The accumulation of some acids, such as fumaric, malic and succinic acid, are believed to involve CO2-fixation which gives high yields of products. The application of special fermentation techniques and the methods for downstream processing of products are described. Techniques such as simultaneous fermentation and product recovery and downstream processing are likely to occupy an important role in the reduction of production costs. Finally, some aspects of process design and current industrial production processes are discussed.

Aspartic Acid↗

Thiodiglycolic acid is excreted by humans receiving ifosfamide and inhibits mitochondrial function in rats.

Thiodiglycolic acid has been identified as a major metabolite of the anticancer drug ifosfamide in humans. Patients treated with 12-16 g ifosfamide/m2.day excreted thiodiglycolic acid ranging from 0.10 +/- 0.02 mmol on the first day of therapy, to a maximum of 3.27 +/- 0.15 mmol on the fourth day of ifosfamide infusion. This amounted to 5.4 +/- 0.2% of the administered dose of ifosfamide appearing as thiodiglycolic acid in urine during a 5 days' continuous ifosfamide infusion. Thiodiglycolic acid (50mg/kg) administered to rats inhibited the carnitine-dependent oxidation of [1-14C]palmitic acid by 55%, but affected neither the oxidation of [1-14C]octanoic acid, which is carnitine-independent, nor the oxidation of [1, 4-14C]succinic acid, a marker of Kreb's cycle activity. Additionally, thiodiglycolic acid (30 microM) inhibited oxidation of palmitic acid but not palmitoyl-L-carnitine in isolated rat liver mitochondria, indicating that it either sequesters carnitine or inhibits carnitine palmitoyltransferase I. This study elucidates a specific mitochondrial dysfunction induced by thiodiglycolic acid which may contribute to the adverse effects associated with ifosfamide chemotherapy.

Animals↗

Heterotrophic carbon metabolism by Beggiatoa alba.

The assimilation and metabolism of CO(2) and acetate by Beggiatoa alba strain B18LD was investigated. Although B. alba was shown to require CO(2) for growth, the addition of excess CO(2) (as NaHCO(3)) to the medium in a closed system did not stimulate growth. Approximately 24 to 31% of the methyl-labeled acetate and 38 to 46% of the carboxyl-labeled acetate were oxidized to (14)CO(2) by B. alba. The apparent V(max) values for combined assimilation and oxidation of [2-(14)C]acetate by B. alba were 126 to 202 nmol min(-1) mg of protein(-1) under differing growth conditions. The V(max) values for CO(2) assimilation by heterotrophic and mixotrophic cells were 106 and 131 pmol min(-1) mg of protein(-1), respectively. The low V(max) values for CO(2) assimilation, coupled with the high V(max) values for acetate oxidation, suggested that the required CO(2) was endogenously produced from acetate. Moreover, exogenously supplied acetate was required by B. alba for the fixation of CO(2). From 61 to 73% of the [(14)C]acetate assimilated by washed trichomes was incorporated into lipid. Fifty-five percent of the assimilated [2-(14)C]acetate was incorporated into poly-beta-hydroxybutyric acid. This was consistent with chemical data showing that 56% of the heterotrophic cell dry weight was poly-beta-hydroxybutyric acid. Succinate and CO(2) were incorporated into cell wall material, proteins, lipids, nucleic acids, and amino and organic acids, but not into poly-beta-hydroxybutyric acid. Glutamate and succinate were the major stable products after short-term [1-(14)C]acetate assimilation. Glutamate and aspartate were the first stable (14)CO(2) fixation products, whereas glutamate, a phosphorylated compound, succinate, and aspartate were the major stable (14)CO(2) fixation products over a 30-min period. The CO(2) fixation enzymes isocitrate dehydrogenase (nicotinamide adenine dinucleotide phosphate; reversed) and malate dehydrogenase (nicotinamide adenine dinucleotide phosphate; decarboxylating) were found in cell-free extracts of both mixotrophically grown and heterotrophically grown cells. The data indicate that the typical autotrophic CO(2) fixation mechanisms are absent from B. alba B18LD and that the CO(2) and acetate metabolism pathways are probably linked.

Acetates↗

[Studies on chemical constituents in root tuber of Cynanchum auriculatum].

OBJECTIVE: To study chemical constituents from Cynanchum auriculatum. METHOD: The chemical components were isolated and purified by silca gel, sephedex-LH-20 and ODS column chromatography. The chemical structures were elucidated on the basis of physicochemical properties and spectral data. RESULT: Thirteen compounds were isolated and identified as: caudatin (1), metaplexigenin (2), cynauricuoside A (3), succinic acid (4), azelaic acid (5), wilforibiose (6), sucrose (7), 1-O-hexadecanolenin (8), beta-amyrin acetate (9), cynanchone A (10), acetylquinol (11), beta-sitosterol (12), daucosterol (13). CONCLUSION: Compounds 4-9 were obtained from this plant for the first time.

Cynanchum↗

Calcium gating of H+ fluxes in chloroplasts affects acid-base-driven ATP formation.

In previous work, calcium ions, bound at the lumenal side of the CF0H+ channel, were suggested to keep a H+ flux gating site closed, favoring sequestered domain H+ ions flowing directly into the CF0-CF1 and driving ATP formation by a localized delta approximately mu H+ gradient. Treatments expected to displace Ca++ from binding sites had the effect of allowing H+ ions in the sequestered domains to equilibrate with the lumen, and energy coupling showed delocalized characteristics. The existence of such a gating function implies that a closed-gate configuration would block lumenal H+ ions from entering the CF0-CF1 complex. In this work that prediction was tested using as an assay the dark, acid-base jump ATP formation phenomenon driven by H+ ions derived from succinic acid loaded into the lumen. Chlorpromazine, a photoaffinity probe for many proteins having high-affinity Ca(++)-binding sites, covalently binds to the 8-kDa CF0 subunit in the largest amounts when there is sufficient Ca++ to favor the localized energy coupling mode, i.e., the "gate closed" configuration. Photoaffinity-bound chlorpromazine blocked 50% or more of the succinate-dependent acid-base jump ATP formation, provided that the ionic conditions during the UV photoaffinity treatment were those which favor a localized energy coupling pattern and a higher level of chlorpromazine labeling of the 8-kDa CF0 subunit. Thylakoids held under conditions favoring a delocalized energy coupling mode and less chlorpromazine labeling of the CF0 subunit did not show any inhibition of acid-base jump ATP formation. Chlorpromazine and calmidazolium, another Ca(++)-binding site probe, were also shown to block redox-derived H+ initially released into sequestered domains from entering the lumen, at low levels of domain H+ accumulation, but not at higher H+ uptake levels; ie., the closed gate state can be overcome by sufficiently acidic conditions. That is consistent with the observation that the inhibition of lumenal succinate-dependent ATP formation by photoaffinity-attached chlorpromazine can be reversed by lowering the pH of the acid stage from 5.5 to 4.5. The evidence is consistent with the concept that Ca++ bound at the lumenal side of the CF0 H+ channel can block H+ flux from either direction, consistent with the existence of a molecular structure in the CF0 complex having the properties of a gate for H+ flux across the inner boundary of the CF0. Such a gate could control the expression of localized or delocalized delta approximately mu H+ energy coupling gradients.

Adenosine Triphosphate↗

Regulation of aerobic fermentation in protozoans. VI Comparative biochemistry of pathogenic and nonpathogenic protozoans.

We have investigated the oxidation of carbohydrate by several protozoan organisms. The oxidation is incomplete and results in a mixture of organic acid and carbon dioxide. The phosphofructokinase and pyruvate kinase, enzymes normally under strict metabolic regulation, are not subject to the normal feedback inhibition or activation mechanisms found in other cells. Moreover, our investigations and those of others support the hypothesis that a primary pathway for glucose metabolism is to phosphoenolpyruvic acid and then to oxalacetic acid with subsequent reduction to succinic acid.

Aerobiosis↗

[Whole body autoradiographic localization of dimercaptosuccinic acid per os in mice].

Dimercapto [14C]succinic acid ([14C]DMSA) was given to male mice by ig 233 kBq. The mice were sacrificed by immersion in dry ice/hexane at 1, 3, 9 and 24 h. The distribution and concentration of [14C]DMSA were observed and analysed by whole-body autoradiograph. Higher concentration appeared in oral cavity, esophagus, gastrointestinal contents, liver, kidney and urine at 1 or 3 h. A moderate concentration was seen in blood, bone and skin. A remarkable reduction of radioactivity was found in liver at 9 h, but GI contents, Harderian gland, kidney and urine retained intense distribution. The results indicated that DMSA absorbed rapidly per os and was eliminated by kidney within 24 h. No tissue had a pronounced retention of the [14C]DMSA.

Animals↗

Nonspecific vaginitis and other genital infections in three clinic populations.

Nonspecific vaginitis was present in 37% of 40 patients attending the Special Urology (Sexually Transmitted Disease) Clinic at the Victoria General Hospital, in 23% of 75 patients attending the Family Planning Clinic, and in 23% of 13 patients attending the Prenatal Clinic at the Grace Maternity Hospital in Halifax, Nova Scotia. The mean prevalence was 27%. Subjective complaints of vaginal odor were significantly associated with nonspecific vaginitis (P less than .001), but symptoms of vaginal discharge or vulvar irritation and itching were not. No correlations were found between the presence of nonspecific vaginitis and the isolation of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Trichomonas vaginalis, or vaginal yeast species. The organic acid present in vaginal washings that best correlated with the presence of nonspecific vaginitis was succinic acid.

Acetates↗

Oxygen-transfer strategy and its regulation effects in serine alkaline protease production by Bacillus licheniformis.

The effects of oxygen transfer on the production and product distribution in serine alkaline protease (SAP) fermentation by Bacillus licheniformis and oxygen-transfer strategy in relation to the physiology of the bacilli were investigated on a defined medium with citric acid as sole carbon source in 3.5-dm(3) batch bioreactor systems. By forming a 3 x 3 matrix with the parameters air-inlet rates of Q(O)/V(R) = 0.2, 0.5, 1.0 vvm, and agitation rates of N = 150, 500, 750 min(-1), the effects of oxygen transfer were investigated at nine different conditions. The concentrations of the product SAP and by-products, i.e., neutral protease, alpha-amylase, amino acids, and organic acids, and SAP activities were determined throughout the bioprocess. Among the constant air-flow and agitation-rate fermentations, Q(O)/V(R) = 0.5 vvm, N = 750 min(-1) oxygen-transfer conditions produced maximum SAP activity that was 500 U cm(-3), at t = 37 h. With the increase in Q(O)/V(R) and/or N, Damköhler number that is the oxygen-transfer limitation decreases; and the process passes from oxygen-transfer limited conditions to biochemical-reaction limited conditions. Further increase in SAP activity, A = 680 U cm(-3) was achieved by applying an oxygen-transfer strategy based on the analysis of the data obtained with the constant oxygen-transfer condition experiments, with a step increase in air-inlet rate, from Q(O)/V(R) = 0.2 to Q(O)/V(R) = 0.5 vvm at N = 750 min(-1) constant agitation rate at t = 24 h. Organic acids and amino acids that were excreted to the fermentation medium varied depending on the oxygen-transfer conditions. With the increase in oxygen-transfer rate acetic acid concentration increased; contrarily, with the decrease in the oxygen-transfer rate the TCA-cycle organic acids alpha-ketoglutaric and succinic acids, and gluconic acid were excreted to the fermentation broth; nevertheless, the application of the oxygen-transfer strategy prevented the increase in acetic acid concentration between t = 35-38 h. Under all the oxygen-transfer conditions, the amino acid having the highest concentration and the amino acid that was not excreted to the fermentation broth were lysine and asparagine, respectively; both of which belong to the aspartic acid-group amino acids. Further, this result indicates the requirement of the genetic regulation directed to the aspartic acid-group enzymes for the progress in SAP production in B. licheniformis.

Acetic Acid↗

Porphyrin synthesis in blood cells of patients with erythropoietic protoporphyria.

The protoporphyrin accumulation observed in the red blood cells of patients with erythropoietic protoporphyria can be explained by decreased activity of the enzyme heme synthetase or by increased production of porphyrins in the affected cells. In literature experimental evidence both for a partial heme synthetase deficiency and for increased porphyrin biosynthesis has been presented. In a group of ten patients with erythropoietic protoporphyria the biosynthesis of porphyrins from delta-aminolevulinic acid and from glycine-succinic acid appeared to be normal in peripheral blood cells. These results are consistent with the partial heme synthetase deficiency previously found to be the basic defect of this disease.

Aminolevulinic Acid↗

Mutagenicity of hydrazides of pyrimidine-nucleotide-precursors in the Salmonella-oxygenase test.

Five newly synthesized hydrazides: L-aspartic acid dihydrazide, DL-ureido-succinic acid dihydrazide, DL-dihydroorotic acid hydrazide, orotic acid hydrazide, and 2,2'-anhydro-1-(beta-D-arabinofuranosyl)-orotic acid hydrazide were tested for mutagenicity in the Ames test. All these hydrazides except DL-ureidosuccinic acid dihydrazide were found to be non-mutagenic. The mutagenic activities of the latter compound which causes base-pair substitution was decreased in the presence of metabolic activator.

Animals↗

Absolute configuration of 3-hydroxyadipic acid in human urine.

A method involving derivatization and combined gas chromatography--mass spectrometry has been developed to separate the enantiomers of 3-hydroxyadipic acid. By combining this method with asymmetric synthesis of the same acid, it has been shown that 3-hydroxyadipic acid excreted in urine consists of at least 95% of the L-enantiomer. This finding supports the hypothesis that dicarboxylic acids are degraded by ordinary beta-oxidation, and indicates that adipic acid may be converted into succinic acid.

Adipates↗

Influence of chloride ion exchange on the permeability and drug release of Eudragit RS 30 D films.

The objective of this study was to investigate the permeability of the cationic acrylic copolymer Eudragit RS 30 D as a function of the anionic buffer species of the dissolution media with special emphasis on the chloride ion exchange of the polymer. Indirect impedance measurement on isolated Eudragit RS films was used to investigate the mechanisms controlling membrane permeability. The chloride ion exchange was determined using capillary electrophoresis during dissolution testing of Eudragit RS 30 D-coated theophylline beads. The dissolution media investigated included various concentrations of sodium acetate, succinic acid and di-sodium succinate. The results of this study demonstrated that the degree of polymer swelling and related drug release was a function of the chloride counterion interaction with the polymer's quarternary ammonium groups. Chloride exchange during the dissolution test with other anions including acetate or succinate ions, resulted in significant changes in the polymer diffusion properties. The ion exchange proved to be the responsible mechanism of controlling polymer permeability as a function of anionic species and concentration. The order of anion permeability enhancing effect was acetate>mono-succinate>disuccinate. The ion exchange could be inhibited significantly by the addition of chloride ions to the dissolution medium.

Acrylic Resins↗

Biochemical and microbial changes during the storage of minimally processed cantaloupe.

The effect of storage time on pH, titratable acidity, degrees Brix, organic acids, sugars, amino acids, and color of minimally processed cantaloupe melon (Cucumis melo L. var. reticulatus Naud. cv. Mission) was determined at 4 degrees C and 20 degrees C. Changes in most of the biochemical parameters with storage time were relatively slow at the lower temperature. At 20 degrees C, a 17% loss in soluble solids and a 2-fold increase in acidity occurred after 2 days. Organic acid content also increased considerably with time at this temperature as a result of the production of lactic acid. Oxalic, citric, malic, and succinic acids were the organic acids, and glucose, fructose, and sucrose were the sugars present in the freshly cut cantaloupe. Malic acid concentration decreased concurrently with lactic acid production indicating the possible involvement of anaerobic malo-lactic fermentation along with sugar utilization by lactic acid bacteria. The effect of storage on microbial growth was determined at 4, 10, and 20 degrees C. Gram-negative stained rods grew at a slower rate at 4 degrees C and 10 degrees C than the Gram-positive mesophilic bacteria that dominated microorganism growth at 20 degrees C. Eighteen amino acids were identified in fresh cantaloupe: aspartic acid, glutamic acid, asparagine, serine, glutamine, glycine, histidine, arginine, threonine, alanine, proline, tyrosine, valine, methionine, isoleucine, leucine, phenyl alanine, and lysine. The dominant amino acids were aspartic acid, glutamic acid, arginine, and alanine. Total amino acid content decreased rapidly at 20 degrees C, but only a slight decrease occurred at 4 degrees C after prolonged storage. Changes in lightness (L), chroma, and hue at both temperatures indicate the absence of browning reactions. The results indicate the potential use of lactic acid and lactic acid bacteria as quality control markers in minimally processed fruits.

Bacteria↗

Carboxylic and dicarboxylic acids extracted from crushed magnesium oxide single crystals.

Carboxylic and dicarboxylic acids (glycolic, oxalic, malonic and succinic) have been extracted with tetrahydrofuran (THF) and H2O from large synthetic MgO crystals, crushed to a medium fine powder. The extracts were characterized by infrared spectroscopy and 1H-NMR. The THF extracts were derivatized with tert-butyldimethylsilyl (t-BDMS) for GC-MS analysis. A single crystal separated from the extract was used for an x-ray structure analysis, giving the monoclinic unit cell, space group P21/c with ao = 5.543 A, bo = 8.845 A, co = 5.086 A, and beta = 91.9 degrees, consistent with beta-succinic acid, HOOC(CH2)COOH. The amount of extracted acids is estimated to be of the order of 0.1 to 0.5 mg g-1 MgO. The MgO crystals from which these organic acids were extracted grew from the 2860 degrees C hot melt, saturated with CO/CO2 and H2O, thereby incorporating small amounts of the gaseous components to form a solid solution (ss) with MgO. Upon cooling, the ss becomes supersaturated, causing solute carbon and other solute species to segregate not only to the surface but also internally, to dislocations and subgrain boundaries. The organic acids extracted from the MgO crystals after crushing appear to derive from these segregated solutes that formed C-C, C-H and C-O bonds along dislocations and other defects in the MgO structure, leading to entities that can generically be described as (HxCyOz)n-. The processes underlying the formation of these precursors are fundamental in nature and expected to be operational in any minerals, preferentially those with dense structures, that crystallized in H2O-CO2-laden environments. This opens the possibility that common magmatic and metamorphic rocks when weathering at the surface of a tectonically active planet like Earth may be an important source of abiogenically formed complex organic compounds.

Carboxylic Acids↗