How hyaluronan-protein complexes modulate the hyaluronidase activity: the model.
Hyaluronan (HA) is the substrate of hyaluronidase (HAase). In addition, HA is able to form electrostatic complexes with many proteins, including HAase. Experiments have shown the strong inhibition of the HA hydrolysis catalyzed by HAase when performed at low HAase over HA concentration ratio and under low ionic strength conditions. Non-catalytic P proteins are able to compete with HAase to form electrostatic complexes with HA and thus to modulate HAase activity. We have modeled the HA-HAase-P system by considering the competition between the two complex equilibria HA-P and HA-HAase, the Michaelis-Menten type behavior of HAase, and the non-activity of the electrostatically complexed HAase. Simulations performed by introducing experimental data produce a theoretical behavior similar to the experimental one, including all the atypical phenomena observed: substrate-dependence, enzyme-dependence and protein-dependence of HAase. This shows that our assumptions are sufficient to explain the behavior of the system and allow us to estimate unknown parameters and suggest new developments.
Vincent
Jean-Claude
JC
Laboratoire Polymères, Biopolymères, Surfaces, FRE 3101 CNRS - Université de Rouen, 76821 Mont-Saint-Aignan cedex, France. jean-claude.vincent@univ-rouen.fr
Lenormand
Hélène
H
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D019295:Computational Biology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D009994:Osmolar Concentration; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011506:Proteins; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase