Kinetics of inhibition of rat brain acetylcholinesterase by 3-diethylaminophenyl-N-methyl- and -N-phenylcarbamate methoiodide in vitro

1976 ◽  
Vol 41 (7) ◽  
pp. 1959-1964
Author(s):  
J. Patočka ◽  
J. Bajgar
Keyword(s):  
Rat Brain ◽  
Kinetics Of ◽  
Kinetics Of Inhibition ◽  
Brain Acetylcholinesterase

On the Kinetics of Inhibition of rat-brain Acetylcholine esterase by Sevin

1967 ◽  
Vol 22 (5) ◽  
pp. 505-507 ◽  
Author(s):  
A. Hassan ◽  
F. M. Abdel-Hamid ◽  
M. R. E. Bahig
Keyword(s):  
Rat Brain ◽  
Acetylcholine Esterase ◽  
Biological Degradation ◽  
Irreversible Inhibition ◽  
Rate Of Progression ◽  
Competitive Nature ◽  
Brain Acetylcholine ◽  
Kinetics Of ◽  
Kinetics Of Inhibition ◽  
Brain Acetylcholinesterase

The inhibition of rat-brain acetylcholinesterase with Sevin was shown to be partly reversible. The rate of progression of the irreversible inhibition is extremely slow and follows the kinetics of a unimolecular reaction, with Κ=3.65 · 10-3 min-1 and t 0.5 190 minutes. The reversible inhibition of the enzyme was found to be of competitive nature. The dissociation constant of E — I (Ki) was determined —by two different methods —to be 5.7 and 7.6 · 10-6 Μ. The presence of acetylcholine protects the enzyme against the irreversible attack of Sevin. It is believed that acetylcholine esterase does not participate in the biological degradation of Sevin in the nervous tissue.

scholarly journals In vitro antibacterial activity and in vivo efficacy of sulbactam-durlobactam against pathogenic Burkholderia species

2020 ◽  
pp. AAC.01930-20
Author(s):  
Krisztina M. Papp-Wallace ◽  
Adam B. Shapiro ◽  
Scott A. Becka ◽  
Elise T. Zeiser ◽  
John J. LiPuma ◽  
...  
Keyword(s):  
Human Pathogens ◽  
Minimal Inhibitory Concentrations ◽  
Class A ◽  
In Vitro Antibacterial Activity ◽  
Lung Infections ◽  
Kinetics Of ◽  
Kinetics Of Inhibition ◽  
Inhibitor Combination

The Gram-negative bacterial genus Burkholderia includes several hard-to-treat human pathogens: two biothreat species, B. mallei (causing glanders) and B. pseudomallei (causing melioidosis), and the B. cepacia complex (BCC) and B. gladioli, which cause chronic lung infections in persons with cystic fibrosis. All Burkholderia spp. possess an Ambler class A Pen β-lactamase, which confers resistance to β-lactams. The β-lactam-β-lactamase inhibitor combination sulbactam-durlobactam (SUL-DUR) is in clinical development for the treatment of Acinetobacter infections. Herein, we evaluated SUL-DUR for in vitro and in vivo activity against Burkholderia clinical isolates. We measured minimal inhibitory concentrations (MICs) of SUL-DUR against BCC and B. gladioli (N = 150), B. mallei (N = 30) and B. pseudomallei (N = 28); studied the kinetics of inhibition of the PenA1 β-lactamase from B. multivorans and the PenI β-lactamase from B. pseudomallei by durlobactam; tested for blaPenA1 induction by SUL-DUR; and evaluated in vivo efficacy in a mouse model of melioidosis. SUL-DUR inhibited growth of 87.3% of the BCC and B. gladioli strains and 100% of the B. mallei and B. pseudomallei strains at 4/4 μg/mL. Durlobactam potently inhibited PenA1 and PenI with k2/K values of 3.9 x 106 M−1s−1 and 2.6 x 103 M−1s−1 and Ki app of 15 nM and 241 nM, respectively, by forming highly stable covalent complexes. Neither sulbactam, durlobactam, nor SUL-DUR increased production of PenA1. SUL-DUR demonstrated activity in vivo in a murine melioidosis model. Taken together, these data suggest SUL-DUR may be useful as a treatment for Burkholderia infections.

The in vitro dissociation kinetics of (R,R)-[125I]4IQNB is reflected in the in vivo washout of the radioligand from rat brain

Life Sciences ◽  
1992 ◽  
Vol 50 (9) ◽  
pp. 629-637 ◽  
Author(s):  
Raymond E. Gibson ◽  
Terry Moody ◽  
Timothy A. Schneidau ◽  
Elaine M. Jagoda ◽  
Richard C. Reba
Keyword(s):  
Rat Brain ◽  
Dissociation Kinetics ◽  
Kinetics Of

scholarly journals Studies of the acetylcholinesterase from houseflies (Musca domestica L.) resistant and susceptible to organophosphorus insecticides

1975 ◽  
Vol 149 (2) ◽  
pp. 463-469 ◽  
Author(s):  
A L Devonshire
Keyword(s):  
Musca Domestica ◽  
Rate Constants ◽  
Gel Electrophoresis ◽  
Organophosphorus Compounds ◽  
Organophosphorus Insecticides ◽  
Triton X ◽  
Kinetics Of ◽  
Kinetics Of Inhibition ◽  
Single Enzyme

Acetylcholinesterase from the heads of insecticide-resistant and -susceptible houseflies (Musca domestica L.) was studied in vitro. The enzymes could not be distinguished electrophoretically, and their behaviour on polyacrylamide-disc-gel electrophoresis was influenced by the presence of Triton X-100 in both the homogenate and the gels. In the absence of detergent, the acetylcholinesterase was heterogeneous, but behaved as a single enzyme when it was present. By analogy with studies of acetylcholinesterase from other sources, these observations were attributed to aggregation of the enzyme when not bound by membranes. The enzyme from resistant flies was more slowly inhibited than the susceptible enzyme, bimolecular rate constants (ki) differing by approx. 4-20-fold for a range of organophosphorus compounds. The kinetics of inhibition of acetylcholinesterase were consistent with the results of electrophoresis, i.e. they corresponded to those of a single enzyme in the presence of Triton X-100, but a mixture of enzymes in its absence. The susceptibility of the more sensitive components in these mixtures was determined.

Postnatal development and kinetics of [3H]gaboxadol binding in rat brain: In vitro homogenate binding and quantitative autoradiography

2007 ◽  
Vol 1170 ◽  
pp. 39-47 ◽  
Author(s):  
Anne Friemel ◽  
Bjarke Ebert ◽  
Pete H. Hutson ◽  
Peter Brust ◽  
Karen Nieber ◽  
...  
Keyword(s):  
Rat Brain ◽  
Postnatal Development ◽  
Quantitative Autoradiography ◽  
Kinetics Of

scholarly journals Adenine nucleotides and magnesium ions in relation to control of mammalian cerebral-cortex hexokinase

1969 ◽  
Vol 112 (5) ◽  
pp. 579-586 ◽  
Author(s):  
H S Bachelard ◽  
P. S. G. Goldfarb
Keyword(s):  
Mixed Type ◽  
Competitive Inhibition ◽  
Adenine Nucleotides ◽  
Effective Control ◽  
Magnesium Ions ◽  
Soluble Enzyme ◽  
Kinetics Of ◽  
Kinetics Of Inhibition

1. The kinetics of inhibition of brain soluble cytoplasmic hexokinase by ADP were examined in relation to variations in the concentrations of Mg2+ and ATP. The type of inhibition observed was dependent on the Mg2+/ATP ratio. 2. ADP at Mg2+/ATP ratios 2:1 exhibited inhibition of the ‘mixed’ type; at Mg2+/ATP ratios 1:1 the inhibition appeared to be competitive with regard to ATP. 3. Inhibition by free ATP was observed when the Mg2+/ATP ratio was less than 1:1. The inhibition was also of the ‘mixed’ type with respect to MgATP2−. 4. The inhibitions due to ADP and to free ATP were not additive. The results suggested that there may be up to four sites in the soluble enzyme: for glucose, glucose 6-phosphate, ADP and MgATP2−. 5. The ‘free’ non-particulate intracellular Mg2+ concentration was measured and concluded to be about 1·5mm. 6. The concentrations in vivo of Mg2+ and ATP likely to be accessible to a cytoplasmic enzyme are suggested to be below those that yield maximum hexokinase rates in vitro. The enzymic rates were measured at relevant suboptimum concentrations of Mg2+ and ATP in the presence of ADP. Calculations that included non-competitive inhibition due to glucose 6-phosphate (56–65% at 0·25mm) resulted in net rates very similar to the measured rates for overall glycolysis. This system may therefore provide a basis for effective control of cerebral hexokinase.

Sign in / Sign up

Export Citation Format

Share Document