Biochemical Investigations of Fatty Acid Amide Hydrolase

Scripps Research Institute, La Jolla CA

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Abstract

DESCRIPTION (provided by applicant): Fatty acid amides (FAAs) represent an emerging class of lipid messengers that influence a variety of behavioral responses including pain sensation, anxiety, sleep, and feeding. Genetic and pharmacological studies have demonstrated that fatty acid amide hydrolase (FAAH), an integral membrane enzyme, is the principal regulator of FAA-based signaling events in vivo. FAAH regulates FAA activity by hydrolyzing these neuroactive signaling lipids to their inactive form, thus functionally terminating FAA signaling. The goals of this research proposal are 1) to understand the molecular and cellular mechanisms by which FAAH degrades FAAs and 2) to determine the biochemical effects of blocking degradation of selective FAAs. These goals will be addressed by studying the roles of FAAH channels in substrate selectivity, hydrolysis, and product release and by applying these in vitro results in designing transgenic mice for biochemical analyses.