scholarly journals MgATP-induced inhibition of the adenosine triphosphatase activity of the chloroform-released mitochondrial adenosine triphosphatase

1981 ◽  
Vol 196 (2) ◽  
pp. 433-442 ◽  
Author(s):  
P N Lowe ◽  
R B Beechey
Keyword(s):  
Adenosine Triphosphatase ◽  
Atp Hydrolysis ◽  
Adenine Nucleotide ◽  
Mitochondrial Atpase ◽  
Hydrolysis Process ◽  
Fixed Concentration ◽  
Dependent Inhibition ◽  
Time Dependent Inhibition ◽  
Kinetics Of ◽  
Preincubation Medium

1. Preincubation of the ox heart chloroform-released mitochondrial ATPase with MgATP results in a time-dependent inhibition of ATPase activity. No re-activation occurs when MgATP remains in the preincubation medium. The enzyme activity returns when all the MgATP in the preincubation system has been hydrolysed. 2. The mechanism of the MgATP-induced inhibition was examined. Inhibition occurs on incubation with MgATP or other hydrolysable nucleotides. Incubation with MgADP or Pi does not cause any inhibition. Neither freshly bound adenine nucleotide nor Pi is associated with inhibited enzyme. The rate of MgATP-induced inhibition correlates with the rate of ATP hydrolysis in the preincubation medium. Changing the rate of ATP hydrolysis at a fixed concentration of ATP also changes the rate of MgATP-induced inhibition by the same proportion. The inhibition is thus related to the ATP-hydrolysis process itself. 3. We propose that intermediate enzyme species of the ATP-hydrolytic sequence can undergo a conformational change to form inhibited species. The kinetics of the inhibition suggest that a substrate-activation step is involved in ATP hydrolysis and MgATP-induced inhibition. 4. The effects of the nature of the preincubation medium on the process of MgATP-induced inhibition and its reversal were examined.

Characterization of the rat Na+/H+ exchanger isoform NHE4 and localization in rat hippocampus

1996 ◽  
Vol 271 (5) ◽  
pp. C1629-C1638 ◽  
Author(s):  
C. Bookstein ◽  
M. W. Musch ◽  
A. DePaoli ◽  
Y. Xie ◽  
K. Rabenau ◽  
...  
Keyword(s):  
Maximum Velocity ◽  
Rat Hippocampus ◽  
Cell Shrinkage ◽  
Cell Functions ◽  
Dependent Inhibition ◽  
Dimethyl Amiloride ◽  
Collecting Tubules ◽  
Time Dependent Inhibition ◽  
Kinetics Of

The kinetics of the Na+/H+ exchanger (NHE) isoform NHE4 were studied by measuring 22Na+ fluxes in stably transfected NHE-deficient fibroblasts. Unlike NHE1, NHE2, and NHE3, activation of this isoform is dependent on hyperosmolarity-induced cell shrinkage. It is virtually inactive at isosmolarity and most active at 490 mosM. When induced by cell shrinkage, NHE4 exhibits a sigmoidal response to increasing extracellular Na+ concentrations, suggesting allosteric or cooperative binding kinetics. In comparison, NHE1 and -3 exhibit hyperbolic velocity vs. extracellular Na+ concentration responses at both iso- and hyperosmolar conditions. Unlike NHE1 and NHE4, hyperosmolarity-induced cell shrinkage inhibits NHE3 activity in transfected fibroblasts, reducing maximum velocity by 40%, with no effect on binding affinity to extracellular Na+.NHE4 is relatively insensitive to inhibition by amiloride analogues in the order 5-(N,N-dimethyl)amiloride > 5-(N,N-hexamethylene)amiloride ride > amiloride > 5-(N-ethyl-N-isopropyl)amiloride. Time-dependent inhibition of activity by cytochalasin D suggests a relationship between the actin cytoskeleton and regulation by cell shrinkage. By in situ hybridization of fixed tissues, NHE4 mRNA was found to be highly expressed in the cavi amnoni fields of rat hippocampus. The kinetics of this exchanger, when considered with its unusual tissue distribution in renal inner medullary collecting tubules and hippocampus, are-consistent with NHE4 having a specialized role in cell functions.

scholarly journals The equilibrium assumption is valid for the kinetic treatment of most time-dependent protein-modification reactions

1979 ◽  
Vol 181 (3) ◽  
pp. 775-778 ◽  
Author(s):  
K Brocklehurst
Keyword(s):  
Rate Constant ◽  
Protein Modification ◽  
Order Rate Constant ◽  
Time Dependent ◽  
Quasi Equilibrium ◽  
Dependent Inhibition ◽  
Dependent Protein ◽  
Time Dependent Inhibition ◽  
Kinetics Of ◽  
Kinetic Treatment

To facilitate mechanistic interpretation of the kinetics of time-dependent inhibition of enzymes and of similar protein modification reactions, it is important to know when the equilibrium assumption may be applied to the model: formula: (see text). The conventional criterion of quasi-equilibrium, k + 2 less than k-1, is not always easy to assess, particularly when k + 2 cannot be separately determined. It is demonstrated that the condition k + 2 less than k-1 is necessarily true, however, when the value of the apparent second-order rate constant for the modification reaction is much smaller than the value of k + 1. Since k + 1 is commonly at least 10(7)M-1.S-1 for substrates, it is probable that the equilibrium assumption may be properly applied to most irreversible inhibitions and modification reactions.

scholarly journals 4-Phenethyl-1-Propargylpiperidine-Derived Dual Inhibitors of Butyrylcholinesterase and Monoamine Oxidase B

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4118
Author(s):  
Tjaša Mazej ◽  
Damijan Knez ◽  
Anže Meden ◽  
Stanislav Gobec ◽  
Matej Sova
Keyword(s):  
Monoamine Oxidase ◽  
Docking Studies ◽  
Monoamine Oxidase B ◽  
Mao B ◽  
Initial Expectation ◽  
Excellent Starting Point ◽  
Starting Point ◽  
Dependent Inhibition ◽  
Dual Inhibitors ◽  
Time Dependent Inhibition

The multi-target-directed ligands (MTDLs) strategy is encouraged for the development of novel modulators targeting multiple pathways in the neurodegenerative cascade typical for Alzheimer’s disease (AD). Based on the structure of an in-house irreversible monoamine oxidase B (MAO-B) inhibitor, we aimed to introduce a carbamate moiety on the aromatic ring to impart cholinesterase (ChE) inhibition, and to furnish multifunctional ligands targeting two enzymes that are intricately involved in AD pathobiology. In this study, we synthesized three dual hMAO-B/hBChE inhibitors 13–15, with compound 15 exhibiting balanced, low micromolar inhibition of hMAO-B (IC50 of 4.3 µM) and hBChE (IC50 of 8.5 µM). The docking studies and time-dependent inhibition of hBChE confirmed the initial expectation that the introduced carbamate moiety is responsible for covalent inhibition. Therefore, dual-acting compound 15 represents an excellent starting point for further optimization of balanced MTDLs.

Sign in / Sign up

Export Citation Format

Share Document