FAAH

Fatty acid 2-hydroxylase
Identifiers
EC number	1.14.18.6
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Search PMC articles PubMed articles NCBI proteins

Fatty acid 2-hydroxylase (FA2H) is an enzyme that plays a crucial role in the metabolism of fatty acids, specifically in the hydroxylation of fatty acids at the 2-position. This enzyme is encoded by the FA2H gene in humans and is involved in the synthesis of 2-hydroxy fatty acids, which are important components of sphingolipids and cerebrosides.

Function

FA2H is responsible for the introduction of a hydroxyl group at the 2-position of fatty acids. This modification is essential for the production of 2-hydroxy fatty acids, which are integral to the structure and function of certain types of lipids, particularly in the nervous system. These lipids are critical for the formation and maintenance of myelin, the protective sheath that surrounds nerve fibers.

Genetics

The FA2H gene is located on chromosome 16q23.1 in humans. Mutations in this gene have been associated with various neurological disorders, including spastic paraplegia and leukodystrophy. These conditions are characterized by defects in myelin formation, leading to progressive neurological impairment.

Clinical Significance

Deficiencies in FA2H activity can lead to a range of neurological disorders due to the disruption of normal myelin synthesis. The enzyme's role in the hydroxylation of fatty acids is crucial for maintaining the integrity of myelin, and its dysfunction can result in demyelinating diseases. Research into FA2H and its associated pathways is ongoing, with the aim of developing therapeutic strategies for conditions linked to its deficiency.

Biochemical Pathway

FA2H is part of the cytochrome P450 family of enzymes, which are involved in the oxidation of organic substances. The enzyme utilizes molecular oxygen to hydroxylate fatty acids, a reaction that requires NADPH as a cofactor. The hydroxylation process is a key step in the biosynthesis of complex lipids that are essential for cellular function and signaling.

Research and Development

Current research on FA2H focuses on understanding its role in lipid metabolism and its implications in neurological diseases. Studies are exploring the potential for gene therapy and other molecular interventions to correct FA2H deficiencies and restore normal lipid function in affected individuals.

Also see

• Sphingolipid metabolism
• Myelin
• Leukodystrophy
• Spastic paraplegia
• Cytochrome P450