Methoxy arachidonyl fluorophosphonate

Methoxy arachidonyl fluorophosphonate (MAFP) is a potent and irreversible inhibitor of several key enzymes in the metabolism of fatty acids, including phospholipase A2, fatty acid amide hydrolase (FAAH), and monoacylglycerol lipase (MAGL). It is often used in biochemical research to study the role of these enzymes in physiological and pathological processes.

Chemical Structure

MAFP is a fluorophosphonate, a class of compounds characterized by a phosphorus-fluorine bond. This bond is highly reactive, allowing MAFP to bind covalently to the active site of target enzymes, thereby inhibiting their activity. The methoxy arachidonyl moiety of MAFP is a long-chain polyunsaturated fatty acid, which allows the compound to interact with lipid substrates and membranes.

Mechanism of Action

MAFP acts by binding irreversibly to the active site of its target enzymes. The fluorophosphonate group reacts with a serine residue in the active site, forming a covalent bond that permanently blocks the enzyme's activity. This mechanism is similar to that of other serine hydrolase inhibitors, such as diisopropyl fluorophosphate (DFP) and sarin.

Biological Effects

The inhibition of phospholipase A2, FAAH, and MAGL by MAFP has profound effects on the metabolism of fatty acids. These enzymes are involved in the production and degradation of various lipid mediators, including eicosanoids and endocannabinoids. By inhibiting these enzymes, MAFP can alter the levels of these mediators, affecting a wide range of physiological processes, such as inflammation, pain perception, and neurotransmission.

Research Applications

MAFP is widely used in biochemical research to study the role of phospholipase A2, FAAH, and MAGL in health and disease. For example, it has been used to investigate the role of endocannabinoids in neuropsychiatric disorders, the involvement of eicosanoids in inflammation and cancer, and the function of lipid mediators in cell signaling.

Safety

As an irreversible inhibitor of key metabolic enzymes, MAFP can have toxic effects. It should be handled with care, using appropriate safety measures to avoid exposure.