Effect of L-cycloserine on brain GABA metabolism

1978 ◽  
Vol 56 (1) ◽  
pp. 62-68 ◽  
Author(s):  
J. D. Wood ◽  
S. J. Peesker ◽  
D. K. J. Gorecki ◽  
D. Tsui
Keyword(s):  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Acid Decarboxylase ◽  
Dramatic Decrease ◽  
Gaba Metabolism ◽  
Time Period ◽  
Gaba Content ◽  
Brain Gaba ◽  
Prior Administration

The administration of L-cycloserine to mice resulted in a dramatic decrease in the activities of 4-aminobutyrate:2-oxoglutarate aminotransferase (GABA-T) and L-alanine:2-oxoglutarate aminotransferase (ALA-T) in both brain and liver, L-Aspartate:2-oxoglutarate aminotransferase was inhibited only slightly, and brain glutamic acid decarboxylase not at all. Liver ALA-T activity returned to near normal levels within 24 h of L-cycloserine administration whereas liver GABA-T and brain ALA-T activities had returned only halfway to normal levels in the same time period. The recovery in the activity of brain GABA-T was even slower. A consequence of the inhibition of brain GABA-T activity was an elevation in the GABA content of the tissue which was maximal 3 h after L-cycloserine administration and which was still noticeable 8 h after the drug treatment. L-cycloserine was also a potent in vitro inhibitor of brain GABA-T activity. The inhibition was competitive with respect to GABA, the Ki value being 3.1 × 10−5 M. The prior administration of L-cycloserine to mice significantly delayed the onset of isonicotinic acid hydrazide induced convulsions.

A dual mechanism for the anticonvulsant action of aminooxyacetic acid

1976 ◽  
Vol 54 (4) ◽  
pp. 534-540 ◽  
Author(s):  
J. D. Wood ◽  
S. J. Peesker
Keyword(s):  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Aminobutyric Acid ◽  
Aminooxyacetic Acid ◽  
Acid Decarboxylase ◽  
Decarboxylase Activity ◽  
Anticonvulsant Action ◽  
Gaba Metabolism ◽  
Dual Mechanism ◽  
The Brain

The intramuscular injection of aminooxyacetic acid (AOAA) into mice elevated the concentration of γ-aminobutyric acid (GABA) in the brain, inhibited glutamic acid decarboxylase activity and delayed the onset of isonicotinic acid hydrazide induced seizures. Analyses of these results and of those obtained previously by the authors and other workers indicated that the anticonvulsant action of AOAA involved two mechanisms. One, involving GABA metabolism, was most effective 6 h after AOAA administration, and the other, not involving GABA, was maximally effective 1.5 h after AOAA injection and was completely absent after 6 h. Depending on the convulsant agent under study, the mechanism of the anticonvulsant action of AOAA was purely of the GABA type, purely of the non-GABA type or a combination of both types.

Hybrid Design of Isonicotinic Acid Hydrazide Derivatives: Machine Learning Studies, Synthesis and Biological Evaluation of their Antituberculosis Activity

2020 ◽  
Vol 17 (3) ◽  
pp. 365-375
Author(s):  
Vasyl Kovalishyn ◽  
Diana Hodyna ◽  
Vitaliy O. Sinenko ◽  
Volodymyr Blagodatny ◽  
Ivan Semenyuta ◽  
...  
Keyword(s):  
Machine Learning ◽  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Predictive Ability ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Starting Point ◽  
Binary Classifiers ◽  
Synthesis And Biological Evaluation

Background: Tuberculosis (TB) is an infection disease caused by Mycobacterium tuberculosis (Mtb) bacteria. One of the main causes of mortality from TB is the problem of Mtb resistance to known drugs. Objective: The goal of this work is to identify potent small molecule anti-TB agents by machine learning, synthesis and biological evaluation. Methods: The On-line Chemical Database and Modeling Environment (OCHEM) was used to build predictive machine learning models. Seven compounds were synthesized and tested in vitro for their antitubercular activity against H37Rv and resistant Mtb strains. Results: A set of predictive models was built with OCHEM based on a set of previously synthesized isoniazid (INH) derivatives containing a thiazole core and tested against Mtb. The predictive ability of the models was tested by a 5-fold cross-validation, and resulted in balanced accuracies (BA) of 61–78% for the binary classifiers. Test set validation showed that the models could be instrumental in predicting anti- TB activity with a reasonable accuracy (with BA = 67–79 %) within the applicability domain. Seven designed compounds were synthesized and demonstrated activity against both the H37Rv and multidrugresistant (MDR) Mtb strains resistant to rifampicin and isoniazid. According to the acute toxicity evaluation in Daphnia magna neonates, six compounds were classified as moderately toxic (LD50 in the range of 10−100 mg/L) and one as practically harmless (LD50 in the range of 100−1000 mg/L). Conclusion: The newly identified compounds may represent a starting point for further development of therapies against Mtb. The developed models are available online at OCHEM http://ochem.eu/article/11 1066 and can be used to virtually screen for potential compounds with anti-TB activity.

scholarly journals Lysyl oxidase activity and elastin/glycosaminoglycan interactions in growing chick and rat aortas.

1987 ◽  
Vol 105 (3) ◽  
pp. 1463-1469 ◽  
Author(s):  
C Fornieri ◽  
M Baccarani-Contri ◽  
D Quaglino ◽  
I Pasquali-Ronchetti
Keyword(s):  
Hydrophobic Interactions ◽  
Isonicotinic Acid ◽  
Lysyl Oxidase ◽  
Acid Hydrazide ◽  
Elastic Fibers ◽  
Amino Groups ◽  
Lysine Residues ◽  
Oxidase Inhibition

Hydrophobic tropoelastin molecules aggregate in vitro in physiological conditions and form fibers very similar to natural ones (Bressan, G. M., I. Pasquali Ronchetti, C. Fornieri, F. Mattioli, I. Castellani, and D. Volpin, 1986, J. Ultrastruct. Molec. Struct. Res., 94:209-216). Similar hydrophobic interactions might be operative in in vivo fibrogenesis. Data are presented suggesting that matrix glycosaminoglycans (GAGs) prevent spontaneous tropoelastin aggregation in vivo, at least up to the deamination of lysine residues on tropoelastin by matrix lysyl oxidase. Lysyl oxidase inhibitors beta-aminopropionitrile, aminoacetonitrile, semicarbazide, and isonicotinic acid hydrazide were given to newborn chicks, to chick embryos, and to newborn rats, and the ultrastructural alterations of the aortic elastic fibers were analyzed and compared with the extent of the enzyme inhibition. When inhibition was greater than 65% all chemicals induced alterations of elastic fibers in the form of lateral aggregates of elastin, which were always permeated by cytochemically and immunologically recognizable GAGs. The number and size of the abnormal elastin/GAGs aggregates were proportional to the extent of lysyl oxidase inhibition. The phenomenon was independent of the animal species. All data suggest that, upon inhibition of lysyl oxidase, matrix GAGs remain among elastin molecules during fibrogenesis by binding to positively charged amino groups on elastin. Newly synthesized and secreted tropoelastin has the highest number of free epsilon amino groups, and, therefore, the highest capability of binding to GAGs. These polyanions, by virtue of their great hydration and dispersing power, could prevent random spontaneous aggregation of hydrophobic tropoelastin in the extracellular space.

scholarly journals Regulation of Iron Entry into Reticulocytes. I. Feedback Inhibitory Effect of Heme on Iron Entry into Reticulocytes and on Heme Synthesis

Blood ◽  
1969 ◽  
Vol 33 (5) ◽  
pp. 690-707 ◽  
Author(s):  
P. PONKA ◽  
J. NEUWIRT
Keyword(s):  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Inhibitory Effect ◽  
Isonicotinic Acid Hydrazide ◽  
Simultaneous Addition ◽  
Heme Synthesis ◽  
Free Heme ◽  
Globin Synthesis

Abstract In the presence of hemin 59Fe incorporation into both heme and reticulocytes decreases. Isonicotinic acid hydrazide which inhibits heme synthesis in vitro is shown to increase reticulocyte radioiron uptake. During inhibition of globin synthesis by cycloheximide, reticulocyte radioiron uptake decreases. This decrease is probably caused by free heme which accumulates in reticulocytes after inhibition of globin synthesis. Simultaneous addition of an inhibitor of heme synthesis—isonicotinic acid hydrazide—to reticulocytes treated by cycloheximide decreases the inhibitory effect of this antibiotic on the iron entry into reticulocytes. The authors suppose the feedback linkage by which heme regulates iron entry into reticulocytes.

scholarly journals Synthesis, Characterization and Antimicrobial Activity of Metal Complexes of N-(4-methoxybenzylidene) Isonicotinohydrazone Schiff Base

2019 ◽  
pp. 1-8 ◽  
Author(s):  
Md. Sajjad Hossain ◽  
Farzana Khanm Camellia ◽  
Nayon Uddin ◽  
Md. Kudrat-E-Zahan ◽  
Laila Arjuman Banu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Molar Conductivity ◽  
Human Pathogens ◽  
Gram Negative ◽  
E Coli ◽  
Vis Spectroscopy ◽  
In Vitro Antibacterial Activity

Two complexes of Cu(II) and Ni(II) with the ligand N- (4-methoxybenzylidene) isonicotinohydrazide, having the formula [M(La)2]2+ (M = Cu(II) and Ni(II)) were synthesized. The ligand was synthesized by the condensation of isonicotinic acid hydrazide (isoniazid) with 4- methoxybenzaldehyde (p- anisaldehyde). The complexes were characterized by FTIR, UV-Vis spectroscopy, molar conductivity, magnetic susceptibility and evaluated for their in vitro antibacterial activity against human pathogens like gram negative Escherichia coli (E. coli) and gram positive Bacillus cereus (B. cereus)strains. The results indicate that all complexes consist of N and O coordination with metals has better antimicrobial activity.

The Possible Involvement of an Amino Acid Decarboxylase in the Stimulation of the Pericardial Cells of Periplaneta by the Corpus Cardiacum

1963 ◽  
Vol 40 (2) ◽  
pp. 343-350
Author(s):  
K. G. DAVEY
Keyword(s):  
Amino Acid ◽  
Isonicotinic Acid ◽  
Isolated Heart ◽  
Acid Hydrazide ◽  
Acid Decarboxylase ◽  
Corpus Cardiacum ◽  
Amino Acid Decarboxylase ◽  
Corpora Cardiaca ◽  
Pericardial Cells ◽  
Semicarbazide Hydrochloride

1. Semicarbazide hydrochloride and isonicotinic acid hydrazide, which are both inhibitors of phosphopyridoxal-dependent systems, inhibit the increase in the rate of beating of hearts which is brought about by breis of corpora cardiaca. This inhibition is partially reversed by phosphopyridoxal. 2. Semicarbazide decreases the percentage of argentaffin-positive cells among pericardial cells exposed to breis of corpora cardiaca. 3. DOPA increases the rate of beating of the isolated heart. This increase is mediated by the pericardial cells and is inhibited by semicarbazide. The inhibition by semicarbazide is reversed by phosphopyridoxal. 4. It is suggested, as a working hypothesis, that the hormone from the corpus cardiacum stimulates the pericardial cells to produce an amine from an amino acid by the action of the appropriate amino acid decarboxylase. The hormone intervenes either by causing the cells to produce more of the amino acid, or by unmasking the amino acid which is pictured as being protected from the enzyme in the unstimulated cell.

scholarly journals Evidence for the role of vitamin B-6 as a cofactor of lysyl oxidase

1977 ◽  
Vol 167 (2) ◽  
pp. 463-467 ◽  
Author(s):  
J C Murray ◽  
C I Levene
Keyword(s):  
Enzyme Activity ◽  
Isonicotinic Acid ◽  
Lysyl Oxidase ◽  
Acid Hydrazide ◽  
Single Peak ◽  
Partial Purification ◽  
Vitamin B ◽  
Epiphysial Cartilage

At 24 h after injection of 16-day chick embryos with [C-3H]pyridoxine hydrochloride, some of this label appears in the epiphysial cartilage. Over 35% of this radioactivity appears in the form of [G-3H]pyridoxal and a further 30% as other vitamin B-6 compounds. Partial purification of lysyl oxidase from the labelled epiphysial cartilage reveals a single peak of radioactivity coinciding with a single peak of enzyme activity. On dialysis against phosphate-buffered saline, 75% of this radioactivity is found to be non-diffusible. After incubation with isonicotinic acid hydrazide, a carbonyl reagent that appears to inhibit lysyl oxidase both in vivo and in vitro, a further 70% of the radioactivity is lost, with a roughly corresponding loss of enzyme activity. It is suggested that a form of vitamin B-6 is required as a cofactor of lysyl oxidase, and that this may have important implications in terms of connective-tissue metabolism.

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