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PubMedDate not supplied

[Effect of carbon sources on the biosynthesis of ergot alkaloids and the activity of carbon metabolism enzymes in Penicillium sizovae].

The study was aimed at finding out how different carbon sources influenced the growth of Penicillium sizovae, the biosynthesis of epoxyagroclavine-1 and agroclavine-1 as well as the activity of key enzymes involved in the citric acid cycle, the pentose phosphate pathway and the glyoxylate cycle. The fungal growth was shown to depend on the carbohydrate substrate: it had a two-phase profile when P. sizovae was cultivated on mannitol and glucose, but not on sorbitol. The quantitative content and composition of ergoalkaloids depended on the combination of carbohydrate and organic acid substrates. The overall productivity of the mycelium (epoxyagroclavin-1+agroclavin-1) was highest when mannitol and fumarate were used. A medium with sorbitol and fumaric acid was very selective in terms of epoxyagroclavine-1 synthesis. The high level of alkaloid biosynthesis correlated with the active functioning of the pentose phosphate cycle and with the low activity of the CAC.

Carbon↗
PubMed1986

Contribution to the knowledge of aerobic processes in Taenia crassiceps larvae (Zeder, 1800).

Respiration of homogenates and isolated mitochondria of T. crassiceps larvae was measured. Respiration (about 70%) could be inhibited by cyanide, indicating that an important part is played by classical respiratory chain. When succinate was used as substrate, relatively low respiratory rates were measured, mitochondria showing higher affinity to NADH. Above a half of respiratory rate remained unchanged even at very low oxygen concentrations. Fumarate exhibited inhibitory activity on respiration of T. crassiceps mitochondria. Respiration in which NADH was used as substrate was twice as much more sensitive to inhibition by fumarate than respiration stimulated by succinate.

Animals↗
PubMed1986

Metabolic enhancement of myocardial preservation during cardioplegic arrest.

An experimental study was undertaken to evaluate the relative efficacy of oxygenated versus unoxygenated cardioplegic solutions and to determine if the addition of certain metabolically active substrates to cardioplegic solutions had any effect on myocardial preservation. Sixty-one pigs were divided into seven groups of animals (5 to 15 animals per group). The impact of different cardioplegic vehicles, i.e., crystalloid versus the oxygen-carrying vehicles, blood and Fluosol-DA, on preservation of high-energy phosphates (adenosine triphosphate and creatine phosphate) was examined in the first three animal groups. The influence of Krebs cycle intermediates, i.e., glutamate, malate, succinate and fumarate, on adenosine triphosphate and creatine phosphate preservation was evaluated in the other four animal groups. All hearts underwent 120 minutes of hypothermic cardioplegic arrest at 15 degrees C followed by 60 minutes of normothermic reperfusion. Higher adenosine triphosphate and creatine phosphate levels were maintained during arrest when oxygenated solutions were used as the cardioplegic vehicle and when any of the four intermediates were added to the crystalloid cardioplegic solution, especially succinate and fumarate. During reperfusion, however, adenosine triphosphate levels were uniformly lower than control whereas creatine phosphate levels rose to either control levels or higher in all groups. No significant intergroup difference could be identified during reperfusion. These findings lead to the conclusion that the presence of either oxygen or certain Krebs cycle intermediates enhances the protective effect of hyperkalemic hypothermic cardioplegia on high-energy phosphates during the arrest period only. This enhancement is not maintained during the reperfusion period.

Adenosine Triphosphate↗
PubMedDate not supplied

Simultaneous gas chromatographic determination of carboxylic acids in soft drinks and jams.

A method was developed for simultaneous gas chromatographic determination of sorbic acid, dehydroacetic acid, and benzoic acid used as preservatives, and succinic acid, fumaric acid, malic acid, and tartaric acid used as acidulants in soft drinks and jams. A sample was dissolved in NH4OH-NH4Cl pH 9 buffer solution, and an aliquot of the solution was passed through a QAE-Sephadex A 25 column. The column was washed with water, and the carboxylic acids were eluted with 0.1N HCl. Sorbic acid, dehydroacetic acid, and benzoic acid were extracted with ethyl ether-petroleum ether (1 + 1), and determined on a 5% DEGS + 1% H3PO4 column. Succinic acid, fumaric acid, malic acid, and tartaric acid in the lower layer were derivatized with N,O-bis(trimethylsilyl)acetamide and trimethylchlorosilane, and determined on a 3% SE-30 column. Recoveries from soft drink and jam samples fortified with 0.1% each of 7 carboxylic acids ranged from 92.4 to 102.6% for preservatives, and from 88.1 to 103.2% for acidulants.

Beverages↗
PubMed1979

In vitro sensitivities to antimicrobial drugs of ureaplasmas isolated from the bovine respiratory tract, genital tract and eye.

The sensitivity to 18 antimicrobial drugs was examined for 66 strains of Ureaplasma sp isolated from respiratory tracts of calves suffering from enzootic pneumonia, urinary tracts of bulls and eyes of cows suffering from infectious bovine kerato-conjunctivitis. Furamizole, tiamulin fumarate, erythromycin lactobionate, malidomycin C, doxycycline hydrochloride, kitasamycin tartrate, tylosin tartrate, T-2636C, tetracycline hydrochloride, oxytetracycline hydrochloride, chlortetracycline hydrochloride, oleandomycin phosphate, furazolidone, spiramycin adipate, chloramphenicol and thiophenicol showed strong inhibiting activity on all the test strains. Among them, furamizole, tiamulin fumarate and erythromycin lactobionate were most active. Kanamycin sulphate showed weak activity on all the strains tested. The differences in origin of the test strains did not affect their sensitivity to any of the drugs.

Animals↗
PubMedDate not supplied

[Enzyme activity of the formate hydrogenlyase complex in Citrobacter freundii].

Citrobacter freundii 62 can grow in the absence of oxygen in media containing glucose, peptone, fumarate or malate. When the medium contained fumarate or malate, the culture could grow under anaerobic conditions only in the presence of molecular hydrogen, formate or nitrate. The highest activity of formatehydrogenlyase and hydrogenase was found when C. freundii grew in a medium with glucose and formate. The activity was lower in media with other organic substrates, particularly, in the absence of formate or H2. The activity of hydrogenase was very low in cells grown under aerobic conditions or in the presence of nitrates while the activity of formatehydrogenlyase was not found at all for all practical purposes. The activity of formate dehydrogenase assessed in the presence of methylene blue was rather high irrespective of the conditions under which the culture was grown. However, when the activity of formate dehydrogenase was determined in the presence of benzyl viologen, it was high only in cells grown in the medium with glucose and formate.

Aerobiosis↗
PubMed1983

Effect of chloride ion on the oxygen affinity of hemoglobin York (alpha 2 beta 2(146)Pro) and S-York hybrid hemoglobin (alpha 2 beta S beta York). Role of the beta 82 lysyl and beta 146 histydyl residues in chloride binding to hemoglobin.

We estimated the relative role of various chloride binding sites in determining the oxygen affinity of hemoglobin using abnormal hemoglobins such as Hb York (Hb Y) (alpha 2 beta 2(146)Pro), Hb Malmö (Hb M) (alpha 2 beta 2(97)Gln), and Hb S and chemically modified hemoglobins such as cross-linked Hb S, Hb Y, and asymmetrical SY hemoglobin with bis(3,5-dibromosalicyl)fumarate. The chloride effect on the p50 values of Hb S and Hb M was identical to that of Hb A. In contrast, the effect of chloride on the p50 values of Hb Y was only 20% of that of Hb A. Cross-linking between the two beta 82 lysyl residues with fumarate decreased the chloride effect by 40%. The effect of chloride on cross-linked Hb Y, in which both beta 82 lysyl and beta 146 histidyl residues were modified, was unchanged from that on Hb Y (20% of Hb A). The effect of chloride on the p50 value of SY asymmetrical hybrid hemoglobin was 40% of that of Hb A or Hb S, which is midway between the values obtained for cross-linked Hb S and Hb Y. From these results, the contribution of beta 146 His and beta 82 Lys on oxygen affinity by binding of chloride was calculated to be 40% each; the remaining 20% chloride effect was attributed to alpha 1 Val.

Chlorides↗
PubMed1978

[Morphological, physiological and taxonomic studies of Bacillus azotoformans].

Seventeen strains of the new species Bacillus azotoformans were isolated by enrichment culture in peptone broth inoculated with pasteurized soil and then incubated under N2O at 32 degrees C. The bacterium is a Gram-negative rod, motile with peritrichous flagella, which produces oval spores without exosporia in swollen sporangia. However, the cells have thick walls, mesosomes, and persistent septa characteristic of Gram-positive bacteria. The bacterium lacks fermentative activity, does not attack carbohydrates, has complex growth requirements, and will grow anaerobically only if one of the following electron acceptors is present: NO3-, NO2-, N2O, S4O6--, or fumarate. Nitrate, nitrite, and nitrous oxide are denitrified with the production of N2. The microorganism is mesophilic, gives a positive oxidase reaction, synthesizes a type c cytochrome, and does not hydrolyse gelatin, starch, or "Tween 80." Poly-beta-hydroxybutyric acid is snythesized when the bacterium is grown in a medium containing DL-3-hydroxybutyrate. The following enzymes are present: nitrate reductase A, respiratory nitrite reductase, tetrathionate and fumarate reductases, and L-glutamate dehydrogenase. The following enzymes are absent: thiosulfate reductase, urease, lecithinase, arginine dihydrolase, phenylalanine deaminase, and catalase. For the 17 strains, the mean value of the G = C percent of the DNA is 39.8 +/- 1.2. All the strains are highly similar.

Anaerobiosis↗
PubMed1984

Alternate substrates of dopamine beta-hydroxylase. II. Inhibition by benzyl cyanides and reactivation of inhibited enzyme.

Several ring-substituted benzyl cyanides lead to inactivation of dopamine beta-hydroxylase during catalysis. With m-hydroxybenzyl cyanide, maximal inactivation occurs when an enzyme group with a pK alpha of 6.0 +/- 0.2 is ionized (Colombo, G., Rajashekhar, B., Giedroc, D. P., and Villafranca, J.J. (1984) J. Biol. Chem. 259, 1593-1600). This paper reports studies conducted to determine the stability of inactivated dopamine beta-hydroxylase. Inactivation of the enzyme by m-hydroxybenzyl cyanide at pH 6.4 is halted by lowering the pH to approximately 5.0 with acetate, fumarate, pyridine, or phosphate buffer in the presence of tyramine. However, if tyramine is omitted, reactivation occurs. The extent of reactivation is dependent upon the final pH value and buffer used to adjust the pH. Reactivation is observed as the pH is lowered from 6.4 to below 5.7 with acetate, fumarate, or HCl. With phosphate, reactivation occurs at any pH value from 6.9 to 4.5 but is greater at lower pH values. Thus, inactivation and reactivation have opposite pH dependencies. Also, reactivation is dependent upon the elapsed time of inactivation. At early times, no reactivation is observed when phosphate is used to adjust the pH, but reactivation is observed later in the inactivation reaction. Reactivation to 100% of the original activity does not occur under these conditions. These data suggest at least two inactivation mechanisms by benzyl cyanides: 1) formation of a tightly bound or covalent adduct between dopamine beta-hydroxylase and enzyme-bound mandelonitrile (or a rearranged form of this molecule), and 2) reversible inhibition resulting from cyanide binding to enzyme-Cu2+. Studies with radiolabeled p-hydroxybenzyl cyanide as well as EPR studies of dopamine beta-hydroxylase-Cu2+ are reported in the following paper.

Adrenal Medulla↗
PubMedDate not supplied

[Key Rhodococcus enzymes in the catabolism of aromatic compounds].

The enzyme apparatus involved in the catabolism of aromatic compounds in rhodococci is characterized by the presence of pyrocatechase and protocatechoate-3,4-dioxygenase as principal enzymes cleaving the aromatic cycle. Metapyrocatechase was found in about 30% of the rhodococci. All the enzymes are inducible. The inductor of pyrocatechase seems to be cyc-cys-muconate, and that of protocatechase appears to be 3-oxoadipate. The metapyrocatechase of rhodococci, in contrast to that of Pseudomonas, is not induced by benzoate, p-toluylate, p-xylene and phenol. The activity of metapyrocatechase rises 20-50 times comparing to the basal level only in the presence of p-cresol. The enzyme has a relatively low activity in rhodococci (50-200 nmole per 1 min per 1 mg of protein), though a very high affinity for methylcatechols. The activity of metapyrocatechase with methylcatechols is 2-5 times as high as that with catechol as a substrate, whereas the activity of pyrocatechase with methylcatechols is two times as low as that with catechol as a substrate. Such additional substrates as acetate, glycerol or fumarate have no effect on the qualitative composition of the key enzymes involved in the degradation of aromatic compounds in Rhodococcus carollinus 172. Glucose represses the synthesis of enzymes cleaving the aromatic ring by 100%. Fumarate taken in a 5-fold excess inhibits the activity of catechol oxygenases by 40%; if it is taken in a 1000-fold excess, it inhibits the enzyme activity by 100%.

Catechol 1,2-Dioxygenase↗
PubMed1994

Activation of alpha-1A adrenoceptors mobilizes calcium from the intracellular stores in myocytes from rat portal vein.

Intracellular free Ca++ concentration ([Ca++]i) was monitored using the fluorescence from the dye fura-2-acetoxymethylester in single myocytes from rat portal vein. In the presence of oxodipine (a L-type Ca++ channel inhibitor), norepinephrine (10 microM) evoked transient increases in [Ca++]i which were related to release of Ca++ from intracellular stores. The alpha-1 adrenoceptors mediating intracellular Ca++ release and inositol phosphate accumulation were identified by using subtype-selective agonists and antagonists. Pretreatment with chloroethylclonidine had little effect on the norepinephrine-induced increase in [Ca++]i and inositol phosphate accumulation. In contrast, prazosin, 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane and alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)-amino )- propyl)benzeneacetonitrile fumarate produced a concentration-dependent inhibition of both intracellular Ca++ release and inositol phosphate accumulation. The rank of potency was prazosin > 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane > alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)-amino - propyl) benzeneacetonitrile fumarate. Methoxamine was as effective as norepinephrine but was less potent as shown by the rightward shift of the concentration-response curves. These results indicate that myocytes from rat portal vein express alpha-1A adrenoceptors whose activation stimulates phosphoinositide turnover and release of Ca++ from intracellular stores. The alpha-1A adrenoceptor stimulation of [Ca++]i and subsequent activation of Ca(++)-activated Cl- current was insensitive to intracellular applications of pertussis toxin, but concentration-dependently blocked by intracellular dialysis with a pipette solution containing anti-alpha q/alpha 11 antibody (whole cell recording mode).(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1976

The effect of dioxyphenylalanine (DOPA), amides and some potential sources of energy on the multiplication of Mycobacterium leprae.

The multiplication of 2 out of 3 M. leprae strains on a medium containing substances from digested non-acid-fast microorganisms or even free of them was significally promoted to D-3,4-dihydroxyphenylalanine (DOPA). The following organic substances exerted growth-promoting effects on several strains: 0.02-0.10% concentrations of succinate greater than fumarate greater than alpha-ketoglutarate and acetate greater than glycerol; 0.2% concentrations of citrate and pyruvate greater than isonicotinamide and benzamide greater than lecithin. 0.5% concentrations of oleate greater than citrate greater than pyruvate greater than acetate greater than fumarate greater than succinate; 5.0% concentrations of butanol and butandiol greater than propanol greater than sorbitol greater than ethanol. However, these effects were variable and strains of various origins acted differently. On media containing DOPA, malachite-green (MG) and at least 0.12 x 10(6) microorganisms/ml the following oxidation-reduction reaction was observed: DOPA was oxidized to a brown compound and malachite-green reduced to an almost colourless product. Consequently, the blue-colour of the cultures turned from blue to brown. This DOPA-MG reaction and the inability to grow on conventional media were used for the identification of 10 cultures (inocula directly from patients) as M. leprae, while a DOPA-MG negative patient-strain grew on media employed for cultivable mycobacteria and was not identical with M. leprae, as proved by the foot-pad test in mice.

Amides↗
PubMed1993

[Stereoisomers of 3-methylfentanyl: synthesis, absolute configuration and analgesic activity].

Fractional crystallization of fumarate salt and oxalate salt of the mixture of cis- and trans-N-(3-methyl-4-piperidyl)-aniline (6) gave pure cis-6 x fumarate salt and trans-6 x oxalate salt respectively. Four optically pure 6 were obtained via resolution of cis-6 and trans-6 with D- and L-tartaric acid. Respective reaction of the optically pure 6 with phenylethyl bromide following propionylation gave optically active 3-methylfentanyl (2). The absolute configuration was confirmed: cis-(+)-2 as (3R,4S), cis-(-)-2 as (3S,4R), trans-(+)-2 as (3S,4S), trans-(-)-2 as (3R,4R). Pharmacological results showed that the configuration of two chiral centers in 2 was very important for analgesic potency. The median effective dose (ED50) of cis-(+)-2, which is the most potent among the four isomers, was found to be 0.00767 mg/kg (in mice, ip., hot plate) with 2600 times as potent as morphine while 119 and 1.5 times as potent as cis-(-)-2 and cis-(+/-)-2 respectively. The potency ratio between trans-(+)-2 and morphine was calculated as 450:1, while that between trans-(+)-2 and trans-(-)-2 as 4:1.

Analgesics↗
PubMed1975

Some biochemical aspects of the enzymic transformation of cortisol with Bacillus cereus.

The role of a variety of compounds including organic acids, vitamins, growth promoting substances, purines and pyrimidines in the bioconversion of cortisol with Bacillus cereus was investigated. The transformation of cortisol to prednisolone and pregn-4-en-11beta, 17alpha,20beta, 21-tetrol-3-one was affected by these compounds in different manners. The enzymatic delta1-dehydrogenation reaction was greatly induced with fumarate, menadione, and xanthine treatments. However, the enzymic reduction of the 20-carbonyl to the 20beta-ol was specifically stimulated with fumarate, nicotinic acid amide, and uracil treatments.

Acids↗
PubMed1993

Effect of screw diameter, insertion technique, and bone cement augmentation of pedicular screw fixation strength.

This study investigated (1) the effect of screw diameter and insertion technique in lumbar vertebrae, and insertion site in the sacrum, on the axial pullout force and transverse bending stiffness of pedicle screws, and (2) the effect of bone cement augmentation using polymethylmethacrylate (PMMA) and the biodegradable composite, poly(propylene glycol-fumarate) on axial pullout force and transverse bending stiffness of pedicle screws inserted into lumbar vertebrae. The axial pullout force and transverse bending stiffness of a 6.25-mm Steffee screw and a 6-mm Kluger screw did not differ significantly in vertebral bodies of similar equivalent bone mineral density. The axial pullout force of Schanz screws was significantly increased with a 1-mm increase in screw diameter. However, there was no significant increase in transverse bending stiffness. In the sacrum, an approach through the S1 facet produced significantly higher axial pullout forces and transverse bending stiffness than the approach described by Harrington and Dickson. PMMA and a biodegradable composite bone cement poly(propylene glycol-fumarate) both increased the axial pullout force. PMMA also increased the transverse bending stiffness.

Biomechanical Phenomena↗
PubMed1993

Transcriptional regulation of puc operon expression in Rhodobacter sphaeroides. Involvement of an integration host factor-binding sequence.

The putative overlapping consensus sequences (-129 to -105) for binding of fumarate nitrate reductase regulator- and integration host factor (IHF)-like proteins to puc operon upstream DNA of Rhodobacter sphaeroides was protected from DNase I digestion by purified Escherichia coli IHF. The binding of E. coli IHF to the purported IHF-binding site in the puc upstream DNA is highly sequence-specific. The recorded binding affinity was significantly lower than that of E. coli IHF to the lambda attP site. Employing site-directed changes in the DNA sequence within the -129 to -105 region, a loss in IHF binding, as monitored through gel retardation analysis, was correlated with alterations in puc operon expression monitored through the use of puc::lacZ transcriptional fusions. These results suggest that the IHF-binding site is involved in repression of puc operon transcription by oxygen as well as modulation of puc operon transcription levels by incident light intensity. Mutations specific to the upstream half of the putative fumarate nitrate reductase regulator-binding site of the puc upstream DNA did not show any physiological effects under the experimental conditions employed. Taken together, these studies reveal that the DNA sequence between -129 to -105 may involve facilitation of the interaction between upstream and downstream cis-acting regulatory sequences involved in puc operon expression.

Bacterial Proteins↗
PubMed1993

Expression, purification, and kinetic characterization of recombinant human adenylosuccinate lyase.

Adenylosuccinate adenosine 5'-monophosphate lyase (EC 4.3.2.2; ASL) catalyzes two distinct reactions in adenosine 5'-monophosphate (AMP) biosynthesis. A S413P mutation in ASL segregates with mental retardation in an affected family (Stone, R. L., Aimi, J., Barshop, B. A., Jaeken, J., Van den Berghe, G., Zalkin, H., and Dixon, J. E. (1992) Nature Genet. 1, 59-63). ASL and S413P ASL have been expressed, purified, and kinetically characterized. Lowering the Escherichia coli growth temperature to 25 degrees C and the concentration of inducer, isopropyl-1-thio-beta,D-galactopyranoside, to 40 microM was necessary for synthesis of soluble, tetrameric enzymes. The recombinant enzymes were purified to homogeneity using anion exchange chromatography followed by chromatography on Blue 2A Sepharose. At pH 7.0 and 25 degrees C, the kcat for cleavage of 5-amino-4-imidazole-N-succinocarboxamide ribotide (SAI-CAR) by ASL was 90 s-1 with a Km of 2.35 microM. The kcat for adenylosuccinate (SAMP) cleavage was 97 s-1 with a Km of 1.79 microM. The catalytic mechanism involved one general base catalyst (pK alpha = 6.4) and one general acid catalyst (pK alpha = 7.5). ASL follows an ordered uni-bi reaction mechanism with fumarate released first. 5-Amino-4-imidazolecarboxamide ribotide (AICAR) and AMP were competitive with SAICAR and SAMP (Ki[AICAR] = 11.3 microM; Ki[AMP] = 9.2 microM), whereas fumarate inhibited noncompetitively (Kii = 2.3 mM, Kis = 2.8 mM). The competitive inhibition by AICAR and AMP suggests a single active site that binds both SAICAR and SAMP. The kinetic constants at pH 7.0, 25 degrees C and the kcat/Km versus pH profiles for ASL and S413P ASL were very similar. These results are consistent with S413P being a structural rather than a catalytic defect.

Adenylosuccinate Lyase↗
PubMed1993

A controlled multiphase trial of ketotifen to minimize neurofibroma-associated pain and itching.

BACKGROUND AND DESIGN: Based on potential contributions of mast cells to neurofibroma-associated itching, pain, and tenderness, the mast cell blocker ketotifen fumarate (Zaditen, Sandoz Pharmaceuticals Corp, Hanover, NJ) has been proposed as a treatment for these symptoms. To test the hypothesis that ketotifen decreases neurofibroma-associated itching, pain, and tenderness, data were accumulated from two protocols. The first was an open-label protocol involving 25 patients with relatively severe symptoms (1170 patient-months), and the second was a double-blind protocol involving 27 patients with either relatively mild or severe neurofibroma-associated symptoms (316 patient-months). All subjects received either oral placebo or 2 to 4 mg of ketotifen fumarate per day. Using a scale of 1 to 10, symptoms were measured before, during, and after treatment. RESULTS: Itching severity scores (means) were as follows: for all patients receiving ketotifen, 7.8 before, 2.8 during, and 7.2 after treatment; for ketotifen-treated patients in the double-blind protocol, 6.6 before, 3.9 during, and 6.4 after treatment; and for placebo-treated patients, 6.0 before and 6.0 during treatment. Pain and tenderness severity scores (means) were as follows: for all patients treated with ketotifen, 7.6 before, 3.6 during, and 6.6 after treatment; for double-blind ketotifen-treated patients, 6.3 before, 4.6 during, and 6.1 after treatment; and for placebo-treated patients, 7.9 before and 6.7 during treatment. CONCLUSIONS: Pretreatment, treatment, and posttreatment levels of itching, pain, and tenderness associated with neurofibromas, using both open-label and double-blind protocols, indicate that ketotifen offers a realistic approach to treating these symptoms.

Adult↗