Avtor/Urednik		Goličnik, Marko
Naslov		Mehanizem kooperativnih pojavov pri holinesterazah
Prevedeni naslov		Mechanism of cooperative phenomena by cholinesterases
Tip		monografija
Kraj izdaje		Ljubljana
Založnik		Medicinska fakulteta Medicinska fakulteta
Leto izdaje		2002
Obseg		str. 175
Jezik		slo
Abstrakt		Cholinesterases are hydrolytic enzymes responsible for metabolism of acetylcholine and other choline esters in central nervous system and in case of vertebrates also in other extracellular fluids. They show very sensitive substrate preference and susceptibility to inhibitors. Moreover, exact kinetic studies show very unusual effects in comparison with classical MichaelisMenten enzyme action. DifFerent cholinesterases show more or less intensely expressive homotropic activation at low substrate concentration and homotropic inhibition at high substrate concentrations. The cooperative phenomena by various cholinesterases have been deeply studied in this work. On the basis of our previous experiences we hypothesized that: (i) substrate activation and inhibition are not separated processes but that both phenomena are only concentration dependent variation of homotropic inhibition; (ii) these pseudo-cooperative phenomena are controled by peripheral site of cholinesterases. We assumed that cholinesterases bind substrates at the peripheral site with high affinity not only in case of enzymes which show substrate activation. In addition, our aim was to develope specific experimental approaches for collecting kinetic experimental data and analysis methods for processing them, to enable the interpretation of kinetic details of each individual studied enzyme. Many kinetic experiments were carried out with various Drosophila melanogaster acetylcholinesterase and human butyrylcholinesterase mutants obtained by site directed mutagenesis. Besides the wild type horse serum butyrylcholinesterase has been also studied. Various reversible inhibitors have been applied as probes for kinetic explorations of enzyme active sites. The first step of catalytic process known as acylation of active serine has been investigated by using an ireversible inhibitor. (Abstract truncated at 2000 characters).
Deskriptorji		CHOLINESTERASES KINETICS CHOLINESTERASE INHIBITORS CHOLINESTERASE REACTIVATORS DROSOPHILA MELANOGASTER POINT MUTATION ACETYLCHOLINESTERASE BUTYRYLCHOLINESTERASE TUBOCURARINE MODELS, THEORETICAL MODELS, MOLECULAR