The fatty acid amide hydrolase (FAAH).

Area of Science:

• Biochemistry and Molecular Biology
• Enzymology
• Neuroscience

Background:

• Fatty acid amide hydrolase (FAAH) is a critical enzyme responsible for hydrolyzing bioactive lipids like anandamide.
• Understanding FAAH's function is vital due to its role in lipid signaling pathways and its potential as a drug target.

Purpose of the Study:

• To provide a comprehensive review of fatty acid amide hydrolase (FAAH).
• To discuss FAAH nomenclature, assays, substrate activity, reversibility, and cloning across species.
• To explore FAAH's structure, distribution, and its significance as a drug target for inhibitor development.

Main Methods:

• Review of existing literature on FAAH nomenclature, assays, and substrate characterization.
• Analysis of cloned FAAH sequences and protein structures from various species (rat, mouse, human, pig).
• Compilation and comparison of data on FAAH distribution in organs and brain regions.
• Review of synthesized FAAH inhibitors, assessing their reversibility, potency, and specificity.

Main Results:

• Detailed comparison of FAAH proteins and mRNAs across different species, highlighting conserved regions.
• Characterization of recombinant FAAH, including its amidase, hydrophobic, and proline-rich domains.
• Mapping of FAAH distribution in major organs and brain regions, correlating with cannabinoid receptors.
• Extensive review of FAAH inhibitors developed since 1994, detailing their pharmacological profiles.

Conclusions:

• FAAH is a well-characterized enzyme with conserved structural and functional domains across species.
• FAAH's distribution and its role in lipid hydrolysis underscore its importance in physiological processes.
• The extensive development of FAAH inhibitors confirms its status as a significant drug target.