FAST

Enzyme involved in the degradation of endocannabinoids

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Crystal structure of FAAH

Identifiers
EC number	3.5.1.99
CAS number	152334-59-1
Alt. names
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway

Fatty acid amide hydrolase (FAAH) is an enzyme that plays a critical role in the endocannabinoid system by degrading fatty acid amides, including the endocannabinoid anandamide. FAAH is a member of the serine hydrolase family and is responsible for the hydrolysis of amide bonds in fatty acid amides, converting them into their corresponding acids and amines.

Structure

FAAH is a membrane-bound enzyme that is primarily located in the endoplasmic reticulum of cells. It is a dimeric protein, meaning it consists of two identical subunits. Each subunit contains a catalytic triad composed of serine, histidine, and aspartate residues, which are essential for its enzymatic activity.

Function

FAAH is responsible for the degradation of several bioactive lipids, including anandamide, oleamide, and palmitoylethanolamide. By breaking down these compounds, FAAH regulates their levels in the body and modulates their physiological effects. Anandamide, for example, is a ligand for cannabinoid receptors and plays a role in pain, mood, and appetite regulation. By degrading anandamide, FAAH helps to terminate its signaling.

Clinical Significance

FAAH has been a target for drug development due to its role in the endocannabinoid system. Inhibition of FAAH can lead to increased levels of anandamide and other fatty acid amides, which may have therapeutic benefits in conditions such as pain, anxiety, and inflammation. Several FAAH inhibitors have been developed and tested in clinical trials, although some have faced challenges due to safety concerns.

Genetics

The gene encoding FAAH is located on chromosome 1 in humans. Variations in the FAAH gene have been associated with differences in pain sensitivity and susceptibility to certain psychiatric disorders. The most studied polymorphism is the FAAH C385A variant, which results in a missense mutation that reduces the enzyme's activity.

Research

Ongoing research is exploring the role of FAAH in various physiological and pathological processes. Studies are investigating its involvement in neurodegenerative diseases, cancer, and metabolic disorders. The development of selective FAAH inhibitors continues to be an area of interest for therapeutic intervention.

Also see

• Endocannabinoid system
• Anandamide
• Cannabinoid receptor
• Serine hydrolase
• Pain management