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PubMed1988

The effect of gabaculine on tetrapyrrole biosynthesis and heterotrophic growth in Cyanidium caldarium.

Pigment synthesis in four strains of the unicellular red alga Cyanidium caldarium with different pigment-synthesizing patterns was inhibited in the presence of gabaculine (3-amino-2,3-dihydrobenzoic acid). Parallel inhibition of light-induced chlorophyll and phycocyanin synthesis was observed in strain III-D-2, which only synthesizes pigments in the light. Similar parallel inhibition was observed in the dark in mutant CPD, which is able to synthesize chlorophyll and phycocyanin in the absence of light. Inhibition of pigment synthesis in all strains was overcome by addition of 5-aminolaevulinic acid. Inhibition of phycocyanin synthesis in mutant GGB (unable to synthesize chlorophyll) and inhibition of chlorophyll synthesis in mutant III-C (unable to synthesize phycocyanin) were also observed. Gabaculine also inhibited the heterotrophic growth of C. caldarium in the dark. However, inhibition was overcome after an extended lag period, following which cell growth proceeded at a similar rate to that of control cells not exposed to gabaculine. Heterotrophic growth in cells pre-exposed to gabaculine was not inhibited by subsequent exposure. Possible mechanisms for this adaptation are discussed.

Aminolevulinic Acid↗
PubMed1998

Hepatic zonation of the catabolism of arginine and ornithine in the perfused rat liver.

The metabolism of 14C-labelled arginine and ornithine was studied in the isolated, nonrecirculating, perfused rat liver. The catabolism of these amino acids required ornithine aminotransferase since treatment of rats with gabaculine, an inhibitor of this enzyme, decreased substantially the production of 14CO2 from the 14C-labelled amino acids. In the liver, ornithine aminotransferase is restricted to a small population of hepatocytes proximal to the terminal hepatic vein [Kuo, F.C., Hwu, W.L., Valle, D. and Darnell Jr., J.E. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 9468-9472], i.e. the perivenous subpopulation of hepatocytes. Catabolism of arginine requires arginase to convert arginine to ornithine which can then be catabolized through ornithine aminotransferase. The presence of arginase activity in the perivenous hepatocytes was demonstrated by experiments in which livers were perfused with [14C]arginine in both antegrade and retrograde directions. Identical rates of 14CO2 production were obtained in these experiments, a result which could only occur if the process of arginine catabolism through ornithine aminotransferase can be carried out in its entirety in the perivenous cells.

Animals↗
PubMed1977

Use of aurintricarboxylic acid as an inhibitor of nucleases during nucleic acid isolation.

Aurintricarboxylic acid (ATA) is a general inhibitor of nucleases. ATA has been shown to inhibit the following enzymes in vitro: DNAse I, RNAse A, S1 nuclease, exonuclease III, and restriction endonucleases Sal I, Bam HI, Pst I and Sma I. The observed inhibition is consistent with the proposal by Blumenthal and Landers (BBRC 55, 680, 1973) that most nucleic acid binding proteins will be sensitive to ATA. The action of ATA as a nuclease inhibitor can be used to advantage in the isolation of cellular nucleic acids.

Aurintricarboxylic Acid↗
PubMed1970

Effect of photoperiod and end-of-day light quality on alkaloids and phenolic compounds of tobacco.

Tobacco plants (Nicotiana tabacum L.) were grown on long or short photoperiods followed by 5 minutes of red or far red radiation each day. Plants that received 16-hour photoperiods had a significantly higher concentration of total alkaloids and total phenolics than those that received 8-hour photoperiods. Significantly higher total alkaloid content was found in plants that received red rather than far red radiation last each day. Within each photoperiod, plants that received far red had higher concentrations of soluble phenols, particularly of chlorogenic acid. The interactions among these variables upon alkaloid and phenolic contents are discussed.

Alkaloids↗
PubMed1984

Changes in the amino acid content of nerve endings (synaptosomes) induced by drugs that alter the metabolism of glutamate and gamma-aminobutyric acid.

The study was centered on the changes in the amino acid content of nerve endings (synaptosomes) induced by drugs that alter the metabolism of glutamate or gamma-aminobutyric acid (GABA), and that possess convulsant or anticonvulsant properties. The onset of seizures induced by various convulsant agents was associated with a decreased content of GABA and an increased content of glutamate in synaptosomes. The concurrent administration of pyridoxine prevented both the biochemical changes and the convulsions. The administration of gabaculine to mice resulted in large increases in the GABA content of synaptosomes that were counteracted by decreases in glutamate, glutamine, and aspartate levels such that the total content of the four amino acids remained unchanged. The administration of aminooxyacetic acid (0.91 mmol/kg) resulted initially in seizure activity, but subsequently in an anticonvulsant action. No simple relationship existed between the excitable state of the brain induced by aminooxyacetic acid and the changes in the synaptosomal levels of any of the amino acid transmitters. A hypothesis was, however, formulated that explained the convulsant-cum-anticonvulsant action of aminooxyacetic acid on the basis of compartmentation of GABA within the nerve endings.

Amino Acids↗
PubMed1972

Sweet taste of water induced by artichoke (Cynara scolymus).

Exposure of the tongue to artichoke can make water taste sweet. Two major active components of artichoke are the salts of chlorogenic acid and cynarin. The sweetening of substances by temporarily modifying the tongue, rather than by adding a substance sweet in itself, may provide an alternative to currently used nonnutritive sweeteners.

Chlorogenic Acid↗
PubMed1976

Synthesis of omega-alicyclic fatty acids from cyclic precursors in Bacillus subtilis.

A mutant of Bacillus subtilis synthesizes a variety of omega-alicyclic fatty acids when fed with the respective alicyclic carboxylic acids. These fatty acids are: omega-cyclopropane, omega-cyclobutane, omega-cyclopentane, omega-cyclohexane, and omega-cyclohexene fatty acids. These unusual fatty acids did not lead to an inhibition of growth at 37 degrees C and pH 7. The selective advantage of these fatty acids under extrene conditions was studied in comparison with the acidophilic, thermophilic bacterium B. acidocaldarius, which normally contains a high proportion of omega-cyclohexane fatty acids.

Bacillus↗
PubMed1990

Chorismic acid, a key metabolite in modification of tRNA.

Chorismic acid is the common precursor for the biosynthesis of the three aromatic amino acids as well as for four vitamins. Mutants of Escherichia coli defective in any of the genes involved in the synthesis of chorismic acid are also unable to synthesize uridine 5-oxyacetic acid (cmo5U) and its methyl ester (mcmo5U). Both modified nucleosides are normally present in the wobble position of some tRNA species. Mutants defective in any of the specific pathways leading to phenylalanine, tyrosine, tryptophan, folate, enterochelin, ubiquinone, and menaquinone have normal levels of cmo5U and mcmo5U in their tRNA. The presence of shikimic acid in the growth medium restores the ability of an aroD mutant to synthesize cmo5U, while O-succinylbenzoate, which is an early intermediate in the synthesis of menaquinone, does not. Thus, chorismic acid is a key metabolite in the synthesis of these two modified nucleosides in tRNA. The absence of chorismic acid blocks the formation of cmo5U and mcmo5U at the first step, which might be the formation of 5-hydroxyuridine. This results in an unmodified U in the wobble position of tRNA(1Val) and in most of the tRNAs normally containing cmo5U and mcmo5U. Since cmo5U and mcmo5U are synthesized under anaerobic conditions, the formation of these nucleosides does not require molecular oxygen. One of the carbon atoms of the side chain, --O--CH2--COOH, originates from the methyl group of methionine. The other carbon atom does not originate directly from the C-1 pool, from the carboxyl group methionine, or from bicarbonate. This metabolic link between intermediary metabolism and translation also exists for another member of the family Enterobacteriaceae, Salmonella typhimurium, as well as for the distantly related gram-positive organism Bacillus subtilis.

Bacillus subtilis↗
PubMed1994

Inhibition of trypsin, plasmin, thrombin and kallikrein by various esters of guanidino- and amidino-acids.

Inhibitory effects of various phenolic esters of trans-4-guanidinomethylcyclohexanecarboxylic acid, amidino-piperidine-4-alkanoic acids or trans-4-amidinocyclohexane-4-alkanoic acids on trypsin, thrombin, plasmin and pancreatic kallikrein were examined. Their inhibitory effects were strongly affected by the acid portion and phenolic group constituting the esters. The effects of the acidic portion and phenolic group on the inhibitory effect varied with each protease; they were most effective on thrombin and plasmin and least effective on kallikrein. The inhibitory effect of these esters on trypsin was affected mainly by acid portion.

Amidines↗
PubMed1993

GABA production in rat islets of Langerhans.

Homogenates of pancreatic islets catalyzed breakdown of L-glutamate to GABA with a rate of 0.24 +/- 0.04 nmol.min-1 x mg-1 protein at 37 degrees C. The formation of GABA was stimulated by addition of pyridoxal phosphate in the range 0.05-1 microM (0.97 +/- 0.02 nmol.min-1 x mg protein-1 at a saturating cofactor concentration), which indicates that the process was catalyzed by glutamic acid decarboxylase. The half-maximal effect was obtained with 0.1 microM PLP. Kinetic analyses of the results showed that the Vmax and Km for the reaction were 1.12 nmol.min-1 x mg protein-1 and 0.66 mM, respectively. The pH optimum was 7.0. Subcellular fractionation revealed that 51% of GAD activity was present in the cytosol, 17% in microsomes, 9% in secretory granules, 5% in mitochondria, and 11% in cell debris. Comparison of the kinetic properties of the cytosolic and microsomal forms of the enzyme showed that their Km for glutamate was the same, but that the cytosolic GAD had a lower Km for PLP. GABA synthesis in the nominal absence of PLP was enhanced by malate (twofold increase at 5 mM) and citrate (threefold increase at 5 mM), but was unaffected by ATP and chloride. However, if the islet homogenate was prepared and incubated in the presence of PLP, neither malate nor citrate influenced enzyme activity. Aspartate and AOA were powerful inhibitors of glutamate breakdown. Freshly isolated islets contained approximately 4 mM GABA, whereas the concentration was < 0.1 mM in whole pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1977

Effects of t-AMCHA and EACA on the plasma kallikrein system.

Varied amounts of t-AMCHA or EACA added to non-contact fresh dog plasma generates kininogenase and TAME esterase activities. These phenomena may be abolished by prior addition of lima bean trypsin inhibitor. t-AMCHA or EACA had no effect on partially purified kallikrein, but had a significant inhibitory influence on plasma kininase. The generation of prekallikrein activator with t-AMCHA was ascertained by gel filtration on a Sephadex G-100 column. The blood kinin level increased about 50% one hr after administration of t-AMCHA. It is suggested from these results that t-AMCHA may initiate the true activation of the kallikrein system by activating the Hageman factor.

Aminocaproates↗
PubMed1983

Use of gamma-aminobutyric acid (GABA)-transaminase inhibitors and a GABA uptake inhibitor to investigate the influence of GABA neurons on dopamine-containing amacrine cells of the rat retina.

The effects of inhibiting gamma-aminobutyric acid-transaminase (GABA-T) with aminooxyacetic acid or with gabaculine and inhibiting GABA uptake with nipecotic acid on dopamine (DA) synthesis in the retina of light-exposed rats were studied. 3,4-Dihydroxyphenylalanine (Dopa) accumulation after the inhibition of L-aromatic amino acid decarboxylase with NSD-1015 was used as an index of DA synthesis. The GABA-T inhibitors significantly increased GABA levels in the retina but had no effect on retinal Dopa accumulation in the light. Dopa accumulation was significantly inhibited at a high dosage by nipecotic acid alone and by low dosages of nipecotic acid in rats pretreated with either aminooxyacetic acid or gabaculine. The dosages of nipecotic acid which inhibited Dopa accumulation in the light also inhibited [3H]GABA uptake in the retina. The inhibitory effects of gabaculine and nipecotic acid on Dopa accumulation appeared to occur at least partially via GABA receptors because their action was significantly reversed by the GABA antagonist bicuculline methiodide. These experiments thus suggest that endogenous GABA can suppress the light-evoked increase in DA synthesis in the rat retina and support previous studies which concluded that an inhibitory GABA input may at least partially regulate the activity of the DA neurons in the retina of rats.

4-Aminobutyrate Transaminase↗
PubMed1980

[Anti-inflammatory effect of aluminum or aurin tricarboxylic acid].

The anti-inflammatory effect of aurin tricarboxylic acid is studied in rats after parenteral injection of 20 and 50 mg/kg. Aurin tricarboxylic acid reduces: the carrageenan-induced oedemas in paws, the carragenan-induced pleural effusion, the carragen-induced granulation tissue growth and the Freund adjuvant-induced arthritis. As non steroïdal antiinflammatory drugs, the aurin tricarboxylic acid inhibits (ED50 = 0.34.10-2 M) the human erythrocyte delta aminolevulinic acid dehydratase, a zinc dependent enzyme. A possible interaction between zinc-enzymes and non steroïdal antiinflammatory compounds is suggested.

Animals↗