Tuning Sensitivity to Ectopeptidase Rates in the Rat Hippocampus Using Numerical Simulations

Y. Ou[1], S. Weber[1]
[1]University of Pittsburgh, Pittsburgh, PA, USA
Publié en 2014

We have created and optimized a multiphysics model in COMSOL Multiphysics® software that studies sensitivity to ectopeptidase rates in the rat hippocampus. Ectopeptidases are membrane-bound enzymes whose catalytic domains face the extracellular space (ECS) (Figure 1). They have traditionally been accepted to inactivate peptides from the ECS[1]. Recently, not only can these enzymes activate peptides, some have also been shown to modulate peptides critical to many important physiological processes [2,3]. Our group has successfully developed two generations of sampling techniques to study enzyme activity in intact tissues, which was the first time it has been done[4,5]. Using the calculations as a guide, we were able to determine the Vmax for membrane-bound aminopeptidases that hydrolyzes Leu-enkephalin.

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