Understanding N-acylethanolamine-hydrolyzing acid amidase
Investigating the catabolism of N-palmitoylethanolamine (PEA) can lead to the better understanding the biological roles of this molecule. One such biological role is the local inhibition of inflammation characterized by rapid accumulation of PEA in an infected area. PEA is degraded by N-acylethanolamine-hydrolyzing acid amidase (NAAA) almost as speedily as it is expressed.
The Mariani lab is studying and kinetically characterizing NAAA in hopes to design of potent and selective inhibitors of this enzyme to prevent the degradation. Our lab plans to clone, express and purify recombinant NAAA from rat tissue. Enzyme assays, site directed mutagenesis, and in vivo localization studies will enable us to understand the catabolism of PEA and other N-acylethanolamines as well as ceramides that are important in lipid metabolism. Synthetic inhibitors based on SAR studies of NAAA will be introduced to prolong the anti-inflammatory effects of PEA and will lead to the conception of the biological effects of both NAAA and PEA.
