Alkylglycerol monooxygenase (AGMO)

Alkylglycerol monooxygenase (AGMO) is a tetrahydrobiopterin- and di-iron-dependent enzyme that catalyzes the oxidative cleavage of the O-alkyl bond of ether lipids such as alkylglycerols and lyso-alkylglycerophospholipids, converting them to corresponding glycerol derivatives and fatty aldehydes[1][3][5][6]. AGMO is an integral membrane protein localized to the endoplasmic reticulum and characterized by a fatty acid hydroxylase domain with conserved histidine residues essential for its catalytic activity[1][3]. It represents the only known enzyme for this specific step in ether lipid degradation in humans and is crucial for maintaining ether lipid balance, impacting processes such as membrane composition, signal transduction (e.g., via platelet-activating factor), and cellular energy homeostasis[1][3][5]. Genetic variation in AGMO is associated with susceptibility to several metabolic and developmental disorders, though its full pathophysiological significance is still under investigation[3][5]. No drugs are currently known to directly target AGMO, and its challenging biochemical properties have hampered drug development to date[3][6].

Other names

Alkylglycerol monooxygenaseAGMOTransmembrane protein 195 (TMEM195)FLJ16237glyceryl-ether monooxygenase

Drugs targeting AGMO would modulate ether lipid catabolism by inhibiting or activating the enzyme’s tetrahydrobiopterin-dependent ether bond cleavage[1][3][5][6].