FRAX
FMO5
FMO5 (Flavin-containing monooxygenase 5) is an enzyme that belongs to the family of flavin-containing monooxygenases (FMOs). These enzymes are involved in the oxidative metabolism of a wide variety of xenobiotics, drugs, and endogenous compounds. FMO5, in particular, has been implicated in the metabolism of certain drugs and the regulation of metabolic processes.
Structure and Function
FMO5 is a member of the FMO family, which are NADPH-dependent enzymes that catalyze the oxygenation of soft nucleophilic heteroatom centers in substrates. The enzyme uses flavin adenine dinucleotide (FAD) as a cofactor to facilitate the transfer of an oxygen atom from molecular oxygen to the substrate, forming an N-oxide, S-oxide, or other oxidized product.
FMO5 is distinct from other FMOs in that it does not appear to be involved in the metabolism of typical FMO substrates such as trimethylamine or methimazole. Instead, FMO5 has been suggested to play a role in the regulation of energy homeostasis and metabolic processes, potentially influencing glucose and lipid metabolism.
Genetics
The FMO5 gene is located on chromosome 1q24.3 in humans. It is expressed in various tissues, with notable expression in the liver and gastrointestinal tract. The gene consists of multiple exons and introns, and its expression can be influenced by genetic polymorphisms, which may affect the enzyme's activity and stability.
Clinical Significance
While FMO5 is not as well-studied as other FMOs, emerging research suggests that it may have a role in metabolic diseases. Alterations in FMO5 expression or function could potentially contribute to conditions such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). However, more research is needed to fully elucidate its clinical significance.
Research and Future Directions
Current research is focused on understanding the specific substrates and physiological roles of FMO5. Studies using knockout mice have provided insights into its potential involvement in metabolic regulation. Future research aims to explore the therapeutic potential of targeting FMO5 in metabolic disorders and to further characterize its substrate specificity.
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Contributors: Prab R. Tumpati, MD