FAAH
Description
The FAAH (fatty acid amide hydrolase) is a protein-coding gene located on chromosome 1.
FAAH, also known as Fatty-acid amide hydrolase 1, is an enzyme belonging to the serine hydrolase family. It was first discovered in 1993 for its ability to break down anandamide, a type of N-acylethanolamine. In humans, FAAH is encoded by the FAAH gene. FAAH is an integral membrane hydrolase with a single N-terminal transmembrane domain. It possesses both esterase and amidase activity in vitro. FAAH serves as the primary enzyme responsible for breaking down a class of bioactive lipids known as fatty acid amides (FAAs). These FAAs include anandamide and 2-arachidonoylglycerol, which are endocannabinoids. Other examples include N-oleoylethanolamine and N-palmitoylethanolamine, the sleep-inducing lipid oleamide, and N-acyltaurines, which are agonists of transient receptor potential (TRP) calcium channels. Mice with a genetic knockout of FAAH exhibit significantly elevated levels of N-acylethanolamines and N-acyltaurines in various tissues, especially anandamide. This leads to an analgesic phenotype in these mice, characterized by reduced pain sensitivity in various pain tests. The impaired ability of FAAH knockout mice to degrade anandamide results in supersensitivity to exogenous anandamide, a cannabinoid receptor (CB) agonist.
FAAH breaks down various lipid molecules, including the sleep-inducing lipid oleamide, the endocannabinoid anandamide, and other fatty amides, into their corresponding fatty acids. This hydrolysis regulates the signaling functions of these molecules. FAAH prefers to break down polyunsaturated substrates like anandamide over monounsaturated substrates. It can also break down the endocannabinoid 2-arachidonoylglycerol. In collaboration with PM20D1, FAAH regulates specific sets of intracellular N-fatty acyl amino acids by breaking down amino acid-conjugated fatty acids like N-fatty acyl glycine and N-fatty acyl-L-serine. However, it does not regulate extracellular N-fatty acyl amino acids.
FAAH is also known as FAAH-1, FAAH1, PSAB.
