Phenylalanine Analogues: Potent Inhibitors of Phenylalanine Ammonia-Lyase Are Weak Inhibitors of Phenylalanine-tRNA Synthetases

1994 ◽  
Vol 49 (11-12) ◽  
pp. 781-790 ◽  
Author(s):  
Gerhard Leubner Metzger ◽  
Nikolaus Amrhein
Keyword(s):  
Wheat Germ ◽  
Phenylalanine Ammonia Lyase ◽  
Inhibitory Effect ◽  
Baker’S Yeast ◽  
Baker's Yeast ◽  
Exchange Reactions ◽  
Trna Synthetases ◽  
Different Sources

(1-Amino-2-phenylethyl)phosphonic acid (APEP), (1-amino-2-phenylethyl)phosphonous acid (APEPi), α-aminooxy-β-phenylpropionic acid (AOPP) and several other phenylalanine analogues are potent inhibitors of (S)-phenylalanine ammonia-lyase (PAL) in vitro and in vivo. The ability of these compounds to inhibit (S)-phenylalanine-tRNA synthetases (PRSs) from wheat germ, soybean, and baker’s yeast has been investigated and compared to the inhibition of PAL. APEP and APEPi were found to inhibit the tRNAphe-aminoacylation reactions catalyzed by the three PRSs studied in vitro in a competitive manner with respect to (5)-phenylalanine. (R)-APEP inhibits the PRSs with apparent Ki values of 144 μᴍ for wheat germ (app. Km for (S)-phe 5.2 μᴍ) , 130 μᴍ for soybean (app. Km for (S)-phe 0.9 μᴍ) , and 1096 μᴍ for baker’s yeast (app. Km for (S)-phe 5.5 μᴍ ) . The apparent Ki values for (R)-APEPi are 315 μᴍ , 160 μᴍ , and 117 μᴍ , respectively. APEP and APEPi inhibit the ATPpyrophosphate exchange reactions catalyzed by the PRSs from wheat germ and baker’s yeast, but they are not activated and do not serve as substrates in these reactions. AOPP has no affinity to any of the three PRSs, whereas it is a potent inhibitor of PAL. In light of our in vitro results with PRSs from different sources it appears unlikely that the PAL inhibitors we have studied have any significant inhibitory effect on this essential step in protein synthesis in vivo.

scholarly journals Inhibition of isoleucyl-transfer ribonucleic acid synthetase in Echerichia coli by pseudomonic acid

1978 ◽  
Vol 176 (1) ◽  
pp. 305-318 ◽  
Author(s):  
Julia Hughes ◽  
Graham Mellows
Keyword(s):  
Rna Synthesis ◽  
Inhibitory Effect ◽  
Trna Synthetase ◽  
Threonine Deaminase ◽  
Trna Synthetases ◽  
E Coli ◽  
Naturally Occurring ◽  
Pseudomonic Acid

The mode of action of the antibiotic pseudomonic acid has been studied in Escherichia coli. Pseudomonic acid strongly inhibits protein and RNA synthesis in vivo. The antibiotic had no effect on highly purified DNA-dependent RNA polymerase and showed only a weak inhibitory effect on a poly(U)-directed polyphenylalanine-forming ribosomal preparation. Chloramphenicol reversed inhibition of RNA synthesis in vivo. Pseudomonic acid had little effect on RNA synthesis in a regulatory mutant, E. coli B AS19 RCrel, whereas protein synthesis was strongly inhibited. In pseudomonic acid-treated cells, increased concentrations of ppGpp, pppGpp and ATP were observed, but the GTP pool size decreased, suggesting that inhibition of RNA synthesis is a consequence of the stringent control mechanism imposed by pseudomonic acid-induced deprivation of an amino acid. Of the 20 common amino acids, only isoleucine reversed the inhibitory effect in vivo. The antibiotic was found to be a powerful inhibitor of isoleucyl-tRNA synthetase both in vivo and in vitro. Of seven other tRNA synthetases assayed, only a weak inhibitory effect on phenylalanyl-tRNA synthetase was observed; this presumably accounted for the weak effect on polyphenylalanine formation in a ribosomal preparation. Pseudomonic acid also significantly de-repressed threonine deaminase and transaminase B activity, but not dihydroxyacid dehydratase (isoleucine-biosynthetic enzymes) by decreasing the supply of aminoacylated tRNAIle. Pseudomonic acid is the second naturally occurring inhibitor of bacterial isoleucyl-tRNA synthetase to be discovered, furanomycin being the first.

scholarly journals INHIBITORY EFFECT OF CRUDE EXTRACTS DERIVED FROM AROMATIC PLANTS AGAINST WHITE MOLD OF BRASSICA JUNCEA VAR. TUMIDA

2019 ◽  
Vol 31 (1) ◽  
pp. 35-46
Author(s):  
Seyedmohammadreza Ojaghian ◽  
Meisam Saremi ◽  
Saeid Pashaei
Keyword(s):  
Phenylalanine Ammonia Lyase ◽  
Zingiber Officinale ◽  
Inhibitory Effect ◽  
White Mold ◽  
Plant Leaves ◽  
Aromatic Plants ◽  
Crude Extracts ◽  
Ethanol Extracts

The objective of this study was to evaluate antifungal activity and resistance inducing potential of crude extracts derived from neem (Azadirachta indica) and ginger (Zingiber officinale) against three isolates of Sclerotinia sclerotiorum, the causal agent of mustard white mold under in vitro and in vivo conditions. In addition, enzymatic tests were carried out to assess the effect of crude extracts on activities of resistance-inducing enzymes in mustard leaves. The results showed that ethanol extracts of neem and ginger at concentration 2 g/l were able to reduce mycelial growth of the pathogen (isolate 3) by 61.5 and 44.3%, respectively. The ethanol extracts of neem and ginger at concentration 2 g/l reduced infection radius on plant leaves from 9.7 in control to 3.1 and 3.4, respectively, due to antifungal efficacy. In addition, ethanol extracts of neem and ginger at concentration 2 g/l decreased infection radius (isolate 1) on plant leaves from 9.5 in control to 2.1 and 2.3, respectively, seven days after application. Enzymatic analyses showed significant increase in level of chitinases, β-1,3-glucanase, Phenylalanine ammonia lyase and Peroxidase due to application of ethanol extracts of neem and ginger.

scholarly journals Inhibition of Mycelial Growth of Rhizoctonia Solani by Chitosan in vitro and in vivo

2019 ◽  
Vol 13 (1) ◽  
pp. 156-161
Author(s):  
Sabah R. Mohammed ◽  
Elsayed M. Zeitar ◽  
Ivan D. Eskov
Keyword(s):  
Rhizoctonia Solani ◽  
Mycelial Growth ◽  
Phenylalanine Ammonia Lyase ◽  
Inhibitory Effect ◽  
Black Scurf ◽  
Potato Tubers ◽  
Antifungal Effect ◽  
Poisoned Food Technique

Objective: Evaluate the antifungal effect of chitosan against Rhizoctonia solani in vitro and the possible mechanisms of its induced activity in potato tubers to control black scurf disease. Methods: The in vitro influence of chitosan at different concentrations on mycelial growth of R. solani was tested by using the poisoned food technique in PDA medium. The effect of these concentrations on the development of lesion diameters in tubers inoculated with R. solani mycelium was assayed for 30 days. The concentration that showed the greatest inhibitory effect on lesion diameters was tested to assess the induced activity of defense-related enzymes in the infected tubers. Results: In the poisoned food technique, chitosan at 1% completely inhibited the growth of R. solani mycelium. In vivo tests showed that chitosan treatment at 0.5% effectively controlled the black scurf in tubers inoculated with R. solani mycelium. Chitosan increased the activities of defense-related enzymes such as Peroxidase (POD), Polyphenol Oxidase (PPO) and Phenylalanine Ammonia-lyase (PAL) in treated tubers of tested cultivars. Conclusion: This work demonstrated that chitosan directly inhibited the growth of R. solani, and potentially elicited defense reaction in potato tubers.

scholarly journals Sourdough Bread Made from Wheat and Nontoxic Flours and Started with Selected Lactobacilli Is Tolerated in Celiac Sprue Patients

2004 ◽  
Vol 70 (2) ◽  
pp. 1088-1096 ◽  
Author(s):  
Raffaella Di Cagno ◽  
Maria De Angelis ◽  
Salvatore Auricchio ◽  
Luigi Greco ◽  
Charmaine Clarke ◽  
...  
Keyword(s):  
Baker’S Yeast ◽  
Celiac Sprue ◽  
Baker's Yeast ◽  
Double Blind ◽  
Potent Inducer ◽  
Fermentation Time ◽  
Human T Cell ◽  
Sourdough Bread

ABSTRACT This work was aimed at producing a sourdough bread that is tolerated by celiac sprue (CS) patients. Selected sourdough lactobacilli had specialized peptidases capable of hydrolyzing Pro-rich peptides, including the 33-mer peptide, the most potent inducer of gut-derived human T-cell lines in CS patients. This epitope, the most important in CS, was hydrolyzed completely after treatment with cells and their cytoplasmic extracts (CE). A sourdough made from a mixture of wheat (30%) and nontoxic oat, millet, and buckwheat flours was started with lactobacilli. After 24 h of fermentation, wheat gliadins and low-molecular-mass, alcohol-soluble polypeptides were hydrolyzed almost totally. Proteins were extracted from sourdough and used to produce a peptic-tryptic digest for in vitro agglutination tests on K 562(S) subclone cells of human origin. The minimal agglutinating activity was ca. 250 times higher than that of doughs chemically acidified or started with baker's yeast. Two types of bread, containing ca. 2 g of gluten, were produced with baker's yeast or lactobacilli and CE and used for an in vivo double-blind acute challenge of CS patients. Thirteen of the 17 patients showed a marked alteration of intestinal permeability after ingestion of baker's yeast bread. When fed the sourdough bread, the same 13 patients had values for excreted rhamnose and lactulose that did not differ significantly from the baseline values. The other 4 of the 17 CS patients did not respond to gluten after ingesting the baker's yeast or sourdough bread. These results showed that a bread biotechnology that uses selected lactobacilli, nontoxic flours, and a long fermentation time is a novel tool for decreasing the level of gluten intolerance in humans.

Antitumor effect of a baker's yeast mannan—mitomycin C conjugate against mouse hepatoma, MH134, in vivo and in vitro

1989 ◽  
Vol 11 (2) ◽  
pp. 191-195 ◽  
Author(s):  
Kazuhiro Aizawa ◽  
Tatsuji Matsumoto ◽  
Keiko Tsukada ◽  
Akiko Ito ◽  
Hiromichi Sato ◽  
...  
Keyword(s):  
Mitomycin C ◽  
Antitumor Effect ◽  
Baker’S Yeast ◽  
Baker's Yeast ◽  
Mouse Hepatoma

scholarly journals Sourdough Fermented Breads are More Digestible than Those Started with Baker’s Yeast Alone: An In Vivo Challenge Dissecting Distinct Gastrointestinal Responses

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2954 ◽  
Author(s):  
Carlo Giuseppe Rizzello ◽  
Piero Portincasa ◽  
Marco Montemurro ◽  
Domenica Maria Di Palo ◽  
Michele Pio Lorusso ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Baker’S Yeast ◽  
Baker's Yeast ◽  
Nutritional Indices ◽  
Long Time ◽  
Total Free Amino Acids ◽  
Carbohydrate Digestibility ◽  
Industrial Level

As a staple food, bread digestibility deserves a marked nutritional interest. Combining wide-spectrum characterization of breads, in vitro nutritional indices, and in vivo postprandial markers of gastrointestinal function, we aimed at comparing the digestibility of sourdough and baker’s yeast breads. Microbiological and biochemical data showed the representativeness of the baker´s yeast bread (BYB) and the two sourdough breads (SB and t-SB, mainly differing for the time of fermentation) manufactured at semi-industrial level. All in vitro nutritional indices had the highest scores for sourdough breads. Thirty-six healthy volunteers underwent an in vivo challenge in response to bread ingestion, while monitoring gallbladder, stomach, and oro-cecal motility. SB, made with moderate sourdough acidification, stimulated more appetite and induced lower satiety. t-SB, having the most intense acidic taste, induced the highest fullness perception in the shortest time. Gallbladder response did not differ among breads, while gastric emptying was faster with sourdough breads. Oro-cecal transit was prolonged for BYB and faster for sourdough breads, especially when made with traditional and long-time fermentation (t-SB), whose transit lasted ca. 20 min less than BYB. Differences in carbohydrate digestibility and absorption determined different post-prandial glycaemia responses. Sourdough breads had the lowest values. After ingesting sourdough breads, which had a concentration of total free amino acids markedly higher than that of BYB, the levels in blood plasma were maintained at constantly high levels for extended time.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

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