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Pattern of aliphatic dicarboxylic acids in uremic serum including a new organic acid, 2,4-dimethyladipic acid.

(1) 2,4-Dimethyladipic acid was first identified in normal human urine using gas chromatography-mass spectrometry. Urinary excretion of 2,4-dimethyladipic acid in 7 healthy adults ranged from 4.9 mumol to 14 mumol per 24 h. (2) Succinic acid, adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid were identified in the ultrafiltrate of the blood obtained from a chronic uremic patient using a hemodialyzer. (3) Levels of succinic acid, adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid in uremic serum were determined using a mass fragmentographic technique. Concentration of succinic acid in uremic serum was comparable to that in normal serum, whereas concentrations of adipic acid, 3-methyladipic acid, 2,4-dimethyladipic acid, pimelic acid and azelaic acid were highly elevated in uremic serum.

Adipates↗

Investigation of the denitrification activity of immobilized Pseudomonas butanovora cells in the presence of different organic substrates.

An investigation was made of the effects of variation of the hydraulic retention time (HRT) and the concentrations of three different carbon sources (succinic acid, ethanol and acetic acid) on the denitrification activity of immobilized Pseudomonas butanovora cells. The highest denitrification activity was in all cases measured at a C: N ratio of 6: and a relatively low HRT (2.5 h). The highest denitrification rates were 1.17 kg NO3--N m(-3) d(-1) for succinic acid, 1.63 kg NO3--Nm(-3) d(-1) for ethanol and 1.53kg NO3--Nm(-3) d(-1) for acetic acid. At the same C:N ratios, ethanol and acetic acid proved to be better substrates for the reduction of nitrate and nitrite. The determined optimum C: N ratios were 1.78 +/- 0.31, 0.95 +/- 0.17, 1.76 +/- 0.42 for succinic acid, ethanol and acetic acid, respectively. The optimum C:N ratios for the different substrates did not change in response to an increased flow rate. At a C: N ratio of 3:1 and a HRT of 1.5 h, the immobilized cells did not retain their activity. Apart from the difference in the effectivity between the electron donors, the main influence on the denitrification rate was exerted by the flow rate The results of this study demonstrated that Pseudomonas butanovora can utilize all three of these carbon sources to achieve a high rate of denitrification.

Acetic Acid↗

Biosynthesis of delta-aminolevulinic acid from the intact carbon skeleton of glutamic acid in greening barley.

The customary route in animals and bacteria for delta-aminolevulinic acid biosynthesis is from glycine and succinyl CoA, catalyzed by the enzyme delta-aminolevulinic acid synthetase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37]. Attempts to demonstrate this route in plants have been unsuccessful. Evidence is given for a new enzymic route of synthesis of delta-aminolevulinic acid in plants. This route involves the incorporation of the intact five-carbon skeleton of glutamic acid into delta-aminolevulinic acid. Demonstration of the new pathway in plants has been made by feeding specifically labeled [14C]glutamic acid to etiolated barley shoots greening in the light. In the presence of levulinate, a competitive inhibitor of delta-aminolevulinic acid dehydrastase [porphobilinogen synthase; delta-aminolevulinate hydro-lyase (adding delta-aminolevulinate and cyclizing); EC 4.2.1.24], delta-aminolevulinate accumulates. The delta-aminolevulinate formed was chemically degraded by periodate to formaldehyde and succinic acid. The C5 (formaldehyde) fragment was separated, as the 5,5-dimethyl-1,3-cyclohexanedione (dimedone) derivative, from the C1-C4 (succinic acid) fragment. The C5 atom contained radioactivity predominantly derived from C1 of glutamic acid. Conversely, the labeled C3 and C4 atoms of glutamic acid were found primarily in the succinic acid (C1-C4) fragment of delta-aminolevulinate. This labeling pattern for delta-aminolevulinic acid is consistent with a biosynthetic route utilizing the intact five-carbon skeleton of alpha-ketoglutarate, glutamate, or glutamine, and is inconsistent with the delta-aminolevulinic acid synthetase pathway utilizing glycine and succinyl CoA as precursors.

Aminolevulinic Acid↗

[Gas-liquid chromatography of non-volatile fatty acid produced by "Yersinia enterocolitica" (author's transl)].

The metabolic products (non-volatile fatty acids) of 24 strains belonging to four Yersinia enterocolitica groups (typical, sucrose negative, rhamnose positive, melibiose and rhamnose positive) were examined by gas liquid chromatography. All strains produced lactic, pyruvic and succinic acids. This technique did not allow any classification for taxonomic purpose. The evolution of lactic and succinic acid production was monitored for 72 h in shaked and non-shaked cultures. The concentration of both acids increased in the first 24 h, then decreased and increased again after 38 h. Shaked culture produced a lesser amount of lactic acid than did non-shaked culture. Only traces of succinic acid were detected in shaked culture. The quantities of metabolic products of the four strains grown in five media were significantly different. These observations suggest that the composition of the medium, the bacterial growth, inoculum size, incubation technique and the incubation time are important factors in metabolic production by aeroanerobic bacteria. Only constant results in the face of such varying factors could be of taxonomic value.

Chromatography, Gas↗

Role of extracellular peroxidase in the superoxide production by wheat root cells.

Extracellular peroxidase has been shown to contribute to superoxide production in wounded wheat (Triticum aestivum L. cv. Ljuba) root cells. The superoxide-synthesizing system of root cells was considerably inhibited by KCN and NaN3 and activated by MnCl2 and H2O2. Treatment of roots with salicylic acid and a range of di- and tri-carbonic acids (malic, citric, malonic, fumaric, and succinic acids) stimulated superoxide production in both root cells and extracellular solution. The H2O2-stimulated superoxide production in the extracellular solution was much higher when roots were preincubated with salicylic or succinic acid. Exogenous acids enhanced peroxidase activity in the extracellular solution. Pretreatment of root cells with the detergents trypsin and sodium dodecyl sulfate had similar effects on the peroxidase activity. Significant inhibition of both superoxide production and peroxidase activity by diphenylene iodonium suggests that the specificity of the latter as an inhibitor of NADPH oxidase is doubtful. Results obtained indicate that extra-cellular peroxidase is involved in the superoxide production in wheat root cells. The mobile form of peroxidase can be readily secreted to the apoplastic solution and serve as an emergency enzyme involved in plant wound response.

Adrenochrome↗

[Structuro-kinetic organization of the tricarboxylic acid cycle in the active functioning of mitochondria].

Taking into account structural and functional organization of mitochondrial processes it has been shown that at active work there functions in mitochondria an accelerated mechanism of succinic acid formation via coupling of glutamate-oxalacetate transaminase and alpha-ketoglutaratdehydrogenase. This way is closed up into a cycle with the participation of cytosol transaminases which support influx of glutamate, pyruvate and malic acid into mitochondria. When provision of the mitochondria with the substrate proceeds along the transaminase pathway the initial slow region of the tricarboxylic acid cycle is omitted. Thus at active work a faster course is selected. It permits realization of the advantages of succinate dehydrogenase high activity and of oxidation efficiency of succinic acid generated in mitochondria which is essentially higher than that under oxidation of succinic acid and even more of other substrates of the tricarboxylic acid cycle.

Citric Acid Cycle↗

Bifidobacterium infantis strains with and without a combination of oligofructose and inulin (OFI) attenuate inflammation in DSS-induced colitis in rats.

BACKGROUND: Pathogenesis of inflammatory bowel disease is thought to be through different factors and there is a relationship between the gut flora and the risk of its development. Probiotics can manipulate the microflora in chronic inflammation and may be effective in treating inflammation. Bifidobacterium are saccharolytic and their growth in the gut can be promoted by non-absorbable carbohydrates and its increase in the colon appears to be of benefit. METHODS: Oligofructose and inulin (OFI) alone and the two B. infantis DSM 15158 and DSM 15159 with and without OFI, were fed to Sprague-Dawley rats for 7 days prior to colitis induction and administrations continued for another 7 days with the DSS. Colitis severity assessed using a Disease Activity Index. Samples were collected 7 days after colitis induction, for intestinal bacterial flora, bacterial translocation, short chain fatty acids (SCFAs), myeloperoxidase (MPO), cytokines (IL-1beta, TNF-alpha, IL-10 and TGF-beta) and malondialdehyde (MDA). RESULTS: OFI alone or the B. infantis strains with and without OFI improved significantly the DAI and decreased colonic MPO activity. Colonic tissue IL-1beta decreased significantly in all treated groups except B. infantis DSM 15158. MDA decreased significantly in B. infantis DSM 15159 with and without OFI compared to colitis control. Succinic acid increased significantly in OFI group with and without DSM 15159 compared to all groups. Sum values of propionic, succinic acid and butyric acid increased significantly in all groups compare to the colitis control. Bacterial translocation to mesenteric lymph nodes decreased significantly in all groups compared to colitis control. Translocation to the liver decreased significantly in all groups compare to the colitis control and OFI + B. infantis DSM 15158 groups. CONCLUSION: Administrations of OFI and Bifidobacterium improve DSS-induced acute colitis and have an anti-inflammatory effect. Major differences in effect were observed between the two B. infantis strains as indicated in MDA and succinic acid concentration as well as bacterial translocation rate in synbiotic combinations.

Animals↗

Influence of chelating agents on the toxicity and distribution of beryllium in rats.

The effect of two new chelating agents-Tiron (4,5-dihydroxy-1,3-benzene disulphonic acid disodium salt) and succinic acid--on the mobilization of beryllium was studied. Animals were exposed to beryllium nitrate (1 mg kg(-1) i.p.) daily for 21 days. Administration of beryllium nitrate showed a marked decrease in haemoglobin percentage, blood sugar, serum alkaline phosphatase and serum protein and a significant increase in the activity of transaminases. Tissue protein and glycogen contents and the activity of alkaline phosphatase, adenosine triphosphatase and succinic dehydrogenase showed significantly decreased values, but beryllium nitrate provoked a considerable increase in the activity of acid phosphatase and glucose-6-phosphatase in the vital and reproductive organs. Significant improvement in the haematological and biochemical parameters was observed with Tiron but no therapeutic effect was seen with succinic acid. Atomic absorption spectrophotometry (AAS) also showed a decreased level of beryllium concentration in the liver and kidney after Tiron therapy.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

Comparison in inducing effect on vitamin E deficiency symptoms in chicks between dilauryl succinate and unsaturated fatty acids.

Dilauryl succinate (DLS) and unsaturated fatty acids (UFA) were compared for the effects of inducing vitamin E deficiency symptoms in chicks. Experimental diets containing DLS, UFA and DLS + UFA, respectively, were given to 1-day-old chicks for 28 days. The diet containing DLS but not UFA showed far less increase in peroxide value than those containing UFA or DLS + UFA when left in a battery brooder of 30 degrees. Vitamin E deficiency symptoms in chicks given DLS + UFA were more severe than those in chicks fed either DLS or UFA. No significant difference in vitamin E deficiency symptoms except incidence of encephalomalacia was observed between the chicks given DLS and UFA. Extracting UFA from the diet containing DLS + UFA resulted in the reduction of vitamin E deficiency induction to the same degree as the diet containing DLS. Synthetic antioxidants were effective in alleviating the vitamin E deficiency symptoms in the chicks fed UFA and DLS + UFA, while only slightly effective in those given DLS. It was found that the effects of DLS and UFA can be separated and combined technically and it was suggested that they have different mechanism in inducing vitamin E deficiency.

Animals↗

Organic acids and branched-chain amino acids in body fluids before and after multiple exchange transfusions in maple syrup urine disease.

We successfully treated a critically ill infant with the classical type of maple syrup urine disease by multiple exchange transfusions via a peripheral artery and vein and with positive calorie supplementation in the early stage of therapy. Clinical improvement was definite after the plasma leucine level fell below 1 mmol/l. There was a close linear correlation between plasma concentrations of branched-chain amino acids and their corresponding branched-chain alpha-keto acids and branched-chain alpha-hydroxy acids. alpha-Hydroxy acids were more easily excreted in the urine than alpha-keto acids and amino acids. Our studies on urinary organic acids supported the existence of minor metabolic pathways of branched-chain alpha-keto acids, although they were not thought to be important in eliminating accumulated alpha-keto acids. Urinary excretion of succinic acid and alpha-ketoglutaric acid, which are components of the citric acid cycle, increased transiently during the patient's convalescence. The cerebrospinal fluid/plasma ratios for branched-chain amino acids, alpha-keto acids, and alpha-hydroxy acids were very high before the transfusions and decreased after improvement. The cerebrospinal fluid/plasma ratios for 5-carbon acids, alpha-ketoisovaleric acid and alpha-hydroxyisovaleric acid were much higher than for other branched-chain acids not only in the patient but also in normal controls. Cerebrospinal fluid levels of alpha-ketoisocaproic acid and alpha-hydroxyisovaleric acid were as high as 1 mmol/l in our patient.

Amino Acids, Branched-Chain↗

[Krebs cycle in tissue of rats subjected to combined effect of hypercapnia, hypoxia and cooling].

The content of the Krebs cycle substrates and activity of dehydrogenases corresponding to them were studied in the brain and myocardium tissues of the non-linear male rats adapted to acute hypoxia under conditions of the altered gas medium. The content of malate and succinic acid was studied in the liver and skeletal muscles only. In the brain the total activity of malate dehydrogenase (MDH, EC 1.1.1.37, 1.1.1.39) alpha-ketoglutarate dehydrogenase (KDH, EC 1.2.4.2) pyruvate dehydrogenase (PDH, EC 1.2.4.1) and isocitrate dehydrogenase (ICDH, EC 1.1.1.41-42) is shown to be decreased and kept to be lowered in all the periods of the study. No essential shifts in the activity of these dehydrogenases were found in the myocardium. The activity of succinate dehydrogenase (SDH, EC 1.3.99.1) in both tissues lowers 48 h after the effect of the mentioned factors. Simultaneously the greatest changes in the level of the substrates were observed in the myocardium, in the brain they were less developed. In the liver the content of malate increases without pronounced changes in the amount of succinic acid and in the skeletal muscles the level of malate and succinic acid lowers.

Acclimatization↗

In vitro studies on the oxidation of medium-chain dicarboxylic acids in rat liver.

The degradation of medium-chained dicarboxylic (DC) acids was investigated on purified mitochondria and peroxisomes. Intact organelles were incubated with dodecanedioic acid (DC12), suberic acid (DC8) and adipic acid (DC6), and the production of lower-chained DC-acids and of acetyl-CoA + acetyl-carnitine was monitored. It was shown, that intact peroxisomes could beta-oxidize DC12, DC10, and DC8 at least as far as DC6, while intact mitochondria readily beta-oxidized DC12, and DC10 as far as succinic acid. DC8 and DC6 were not oxidized by intact mitochondria when these two acids were presented externally to the intact organelle. When they were formed intramitochondrially from DC12 and DC10, both DC8 and DC6 were, however, to a great extent beta-oxidized as far as succinic acid. The major reason for this difference between mitochondrial oxidation of externally and internally located DC8 and DC6 seems to be an inability to transport these two acids through the mitochondrial membrane. For DC12 and DC10, the mitochondrial transport systems, which were indicated to be identical to the systems used by the corresponding monocarboxylic acids, were found to be rate-limiting in the beta-oxidation of these acids. A contributing factor to the undetectable beta-oxidation of externally located DC8 and DC6 may also be, that the Km values of DC8-CoA (460 +/- 70 mumol/l) and DC6-CoA (980 +/- 90 mumol/l) towards the acyl-CoA dehydrogenases are very high. These results imply that very high concentrations of intermediates are created intramitochondrially during beta-oxidation, concentrations which are probably only formed through formation of DC8-CoA and DC6-CoA from longer DC-acids and not by transport from outside the mitochondria. The data presented thus for the first time give evidence to a pathway for medium-chained monocarboxylic acids (especially lauric acid and decanoic acid) through cytosolic omega-oxidation followed by activation, transport over the mitochondrial membrane and beta-oxidation to succinic acid.

Acetyl Coenzyme A↗

Effect of pretreatment reagent for enamel on the adhesion of resin composite.

Aqueous solutions of methacryloyl tyrosine amide (MTYA), glyceryl methacrylate (GM), glutaraldehyde and succinic acid were prepared and their effectiveness as pretreatment reagents was evaluated by measuring the tensile bond strengths between resin composite and polished enamel. Pretreatment of polished enamel with MTYA.GM.S3 (A: 6% MTYA + 70% GM aqueous solution, B: 3% succinic acid aqueous solution) gave bond strengths of about 7 MPa, whereas pretreatment with MTYA.G.GM.S3 (A: 6% MTYA + 70% GM aqueous solution, B: 3% succinic acid + 2% glutaraldehyde aqueous solution) gave values of about 5 MPa. The mean bond strengths of each after 60 s of scrubbing with MTYA.GM.S3 or by MTYA.G.GM.S3 were raised to about 9.5 MPa, and the type of bond failure was fracture of the bonding agent. Although there were no resin tags, it was found that resin composite was able to adhere to polished enamel without acid etching.

Acid Etching, Dental↗

Growth of Campylobacter in media supplemented with organic acids.

The growth of Campylobacter spp. in media supplemented with organic acids was examined. A Bioscreen C Microbiology Reader was used to measure growth of cultures incubated at 37 degrees C for 48 h in a tryptose-yeast extract basal broth medium and in basal broth supplemented with 10, 20, 30, 40, or 50 mM citric, fumaric, lactic, malic, or succinic acid. Growth of three of six isolates was significantly greater (P < or = 0.05) in media supplemented with 20 to 50 mM citric acid than in nonsupplemented media, growth of five of six isolates was significantly greater in media supplemented with 10 to 50 mM succinic acid than in nonsupplemented media, and growth of six of six isolates was significantly greater in media supplemented with 10 to 50 mM fumaric or malic acid or with 20 to 50 mM lactic acid than in nonsupplemented media. Isolates were also cultured in basal media supplemented with a mixture of 10, 20, 30, 40, or 50 mM fumaric, malic, lactic, and succinic acids. Results indicated that the growth of all Campylobacter isolates was significantly greater in media supplemented with mixtures containing each of these organic acids at 10 to 40 mM than in nonsupplemented media. These findings indicate that in vitro growth of Campylobacter spp. may be significantly enhancedin media supplemented with organic acids that support the growth of these bacteria.

Acids↗

Comparative antimicrobial activity, in vitro and in vivo, of soft N-chloramine systems and chlorhexidine.

Antimicrobial activity of the following four new N-chloramine compounds was evaluated: two chlorinated simple amino acids, a chlorinated half-ester of succinic acid, and a chlorinated half-ester of glutaric acid. For comparison, the known bactericidal agents 3-chloro-4,4-dimethyl-2-oxazolidinone and chlorhexidine were evaluated by the same procedure. The contact germicidal efficiency screen was used to examine the in vitro bactericidal activity of all six compounds in the absence and presence of 5% horse serum or 5% Triton X-100. The four new compounds were found to have greater germicidal activity than the other compounds tested and to exhibit low toxicity and skin irritation values. The in vivo bactericidal activity was evaluated in two studies. In the occlusion test, three of the four new compounds plus chlorhexidine diacetate were tested. The N-chloramines were significantly superior to chlorhexidine in preventing the expansion of the normal flora under occlusion. In the scrub test, a gloved-hand wash method was used to compare the antimicrobial effect of a 1% solution of the chlorinated half-ester of succinic acid in triacetin with that of a commercial germicidal hand wash containing 4% chlorhexidine gluconate. The two preparations exhibited essentially the same hand-degerming activity.

Animals↗

The effects of organic species on the hygroscopic behaviors of inorganic aerosols.

Water-soluble organic compounds have recently received much attention because of their ability to absorb water and alter the hygroscopic properties of inorganic aerosols. The effects of glycerol, succinic acid, malonic acid, citric acid, and glutaric acid on the water cycles (water activities during particle evaporation and growth), crystallization relative humidities (CRH), and deliquescence relative humidities (DRH) of sodium chloride (NaCl) and ammonium sulfate (AS) were studied using an electrodynamic balance (EDB). The growth factors of these inorganic and organic mixtures were lower than those of the pure inorganic species. The presence of all these organics in the mixed particle reduce the water absorption of NaCl but enhance that of AS relative to that of the pure inorganic salts. Glycerol and succinic acid did not affect the deliquescence properties of NaCl and AS, although succinic acid increased the CRH of NaCl and AS. Malonic acid and citric acid, behaving as nondeliquescent species in single particle studies, caused NaCl and AS particles to absorb a significant amount of water before deliquescence. Glutaric acid caused NaCl and AS to deliquesce gradually, spanning a wide range of relative humidity. The ZSR model was found to be useful in predicting the water activity of the mixtures and the growth ratios. However, the detailed crystallization and deliquescence behaviors of the organic/inorganic mixtures cannot be easily predicted from the hygroscopic properties of the individual components.

Absorption↗

Prevotella marshii sp. nov. and Prevotella baroniae sp. nov., isolated from the human oral cavity.

Eleven strains of anaerobic Gram-negative bacilli isolated from the human oral cavity were subjected to a comprehensive range of phenotypic and genotypic tests and were found to comprise two homogeneous groups, designated E2 and E4. 16S rRNA gene sequence analysis revealed that members of both groups belonged to the genus Prevotella but were distinct from any species with validly published names. This distinction was confirmed by DNA-DNA hybridization and phenotypic tests. Two novel species are therefore proposed: Prevotella marshii sp. nov. (group E2) and Prevotella baroniae (group E4). Both species are saccharolytic; the end-products of fermentation for P. marshii are acetic, propionic and succinic acids, while P. baroniae produces acetic and succinic acids with minor amounts of isovaleric and isobutyric acids. The G+C content of the DNA of the type strain of Prevotella marshii is 51 mol% and that of Prevotella baroniae is 52 mol%. The type strain for P. marshii is E9.34(T) (=DSM 16973(T)=CCUG 50419(T)) and that for P. baroniae is E9.33(T) (=DSM 16972(T)=CCUG 50418(T)).

Bacterial Typing Techniques↗