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.

Disrupting PEA catabolism could indeed
become an effective means
for treatment of inflammation.
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.