Home About us Contact
|
Home About us Contact | ||
|
|
||
Mixed-type Inhibitor (mixed-type + inhibitor)
Selected AbstractsKinetics of inhibition of acetylcholinesterase in the presence of acetonitrileFEBS JOURNAL, Issue 8 2009Markus Pietsch The hydrolysis of acetylthiocholine by acetylcholinesterase from Electrophorus electricus was investigated in the presence of the inhibitors tacrine, gallamine and compound 1. The interaction of the enzyme with the substrate and the inhibitors was characterized by the parameters KI, ,,, b or ,, Km and Vmax, which were determined directly and simultaneously from nonlinear Michaelis,Menten plots. Tacrine was shown to act as a mixed-type inhibitor with a strong noncompetitive component (,, , 1) and to completely block deacylation of the acyl-enzyme. In contrast, acetylcholinesterase inhibition by gallamine followed the ,steric blockade hypothesis', i.e. only substrate association to as well as substrate/product dissociation from the active site were reduced in the presence of the inhibitor. The relative efficiency of the acetylcholinesterase,gallamine complex for the catalysis of substrate conversion was determined to be 1.7,25% of that of the free enzyme. Substrate hydrolysis and the inhibition of acetylcholinesterase were also investigated in the presence of 6% acetonitrile, and a competitive pseudo-inhibition was observed for acetonitrile (KI = 0.25 m). The interaction of acetylcholinesterase with acetonitrile and tacrine or gallamine resulted in a seven- to 10-fold increase in the KI values, whereas the principal mode of inhibition was not affected by the organic solvent. The determination of the inhibitory parameters of compound 1 in the presence of acetonitrile revealed that the substance acts as a hyperbolic mixed-type inhibitor of acetylcholinesterase. The complex formed by the enzyme and the inhibitor still catalysed product formation with 8.7,9.6% relative efficiency. [source] Browning Prevention by Ascorbic Acid and 4-Hexylresorcinol: Different Mechanisms of Action on Polyphenol Oxidase in the Presence and in the Absence of SubstratesJOURNAL OF FOOD SCIENCE, Issue 9 2007E. Arias ABSTRACT:, We have investigated the mechanism of action of 4-hexylresorcinol (4-HR) and ascorbic acid (AA) on the polyphenol oxidase (PPO) catalyzed oxidation of phenolic substrates. Incubation of PPO with 4-HR diminishes strongly PPO activity. This effect can be erroneously interpreted, due to the high affinity of 4-HR for PPO, as irreversible inactivation of PPO. However, PPO activity can be recovered by dialysis after incubation with 4-HR. 4-hexylresorcinol is a canonical enzyme inhibitor that binds preferentially to the oxy form of PPO. It is a mixed-type inhibitor, because it influences both apparent Vmax (1.26 compared with 0.4 units in the absence and presence of 4-HR, respectively) and Km values (0.28 mM compared with 0.97 mM in the absence and in the presence of 4-HR, respectively) of PPO. AA can prevent browning by 2 different mechanisms: In the absence of PPO substrates it inactivates PPO irreversibly, probably through binding to its active site, preferentially in its oxy form. In the presence of PPO substrates, AA reduces PPO oxidized reaction products, which results in a lag phase when measuring PPO activity by monitoring dark product formation but not when monitoring O2 consumption. The simultaneous use of both 4-HR and AA on PPO results in additive prevention of browning. [source] Inhibition of acetylcholinesterase activity by tea tree oil and constituent terpenoidsFLAVOUR AND FRAGRANCE JOURNAL, Issue 2 2006Mitsuo Miyazawa Abstract In vitro inhibition of bovine erythrocyte acetylcholinesterase (AChE) activity by tea tree oil was investigated. The main constituents in the tea tree oil batch used for the analysis of AChE inhibition were terpinen-4-ol (35.6%), , -terpinene (19.5%), , -terpinene (8.3%), p -cymene (7.2%) and 1,8-cineole (4.4%). AChE was measured by a colorimetric method. IC50 values were obtained for tea tree oil and , -pinene and were 51.2 µg/ml and 57.1 µg/ml, respectively. Tea tree oil was found to contain mixed-type inhibitors; a mixture of main constituents and main constituents showed competitive inhibition. Copyright © 2005 John Wiley & Sons, Ltd. [source] Synthesis of New C(2) -Substituted gluco -Configured Tetrahydroimidazopyridines and Their Evaluation as Glucosidase InhibitorsHELVETICA CHIMICA ACTA, Issue 10 2005Bhagavathy Shanmugasundaram The gluco -configured C(2) -substituted tetrahydroimidazopyridines 8,14 were prepared and tested as inhibitors of the , -glucosidases from Caldocellum saccharolyticum and from sweet almonds, and of the , -glucosidase from brewer's yeast. All new imidazopyridines are nanomolar inhibitors of the , -glucosidases and micromolar inhibitors of the , -glucosidase. The 3-phenylpropyl derivative 14 proved the strongest inhibitor of the Caldocellum , -glucosidase (Ki,=,0.9,nM), only slightly weaker than the known 2-phenylethyl analogue 7, and the propyl derivative 13 is the strongest inhibitor of the sweet almond , -glucosidases (Ki,=,3.2,nM), again slightly weaker than 7. There is no strong dependence of the inhibition on the nature of the C(2) -substituent and no clear correlation between the inhibitory strength of the known manno -configured imidazopyridines 2,6 and the gluco -analogues 8,12. While most manno -imidazopyridines are competitive inhibitors, the gluco -analogues proved non-competitive inhibitors of the Caldocellum , -glucosidase and mixed-type or partial mixed-type inhibitors of the sweet almond , -glucosidases. [source] | ||||||||||