FMO5

Flavin-containing monooxygenase 3 (FMO3) is an enzyme that in humans is encoded by the FMO3 gene. This enzyme is part of the flavin-containing monooxygenase family, which is involved in the metabolism of xenobiotics, drugs, and endogenous compounds.

Function

FMO3 is primarily expressed in the liver and is responsible for the N-oxidation of a variety of nitrogen-containing compounds. This enzyme plays a crucial role in the metabolism of trimethylamine (TMA) to trimethylamine N-oxide (TMAO), a process that is important for the detoxification of TMA, which is derived from dietary sources such as choline and carnitine.

Clinical significance

Mutations in the FMO3 gene can lead to a condition known as trimethylaminuria, also known as "fish odor syndrome." This condition is characterized by the accumulation of TMA, which is excreted in sweat, urine, and breath, leading to a strong fishy odor. Trimethylaminuria is an autosomal recessive disorder, meaning that individuals must inherit two defective copies of the FMO3 gene to manifest the condition.

Genetic variations

Several polymorphisms in the FMO3 gene have been identified, some of which are associated with reduced enzyme activity. These polymorphisms can affect the metabolism of drugs and other compounds, potentially influencing drug efficacy and toxicity.

Biochemical properties

FMO3 is a flavoprotein that requires flavin adenine dinucleotide (FAD) as a cofactor. The enzyme catalyzes the oxygenation of substrates by transferring an oxygen atom from molecular oxygen to the substrate, with the concomitant reduction of the other oxygen atom to water.

Research and implications

Recent studies have suggested that TMAO, the product of FMO3 activity, may be involved in the development of cardiovascular diseases. Elevated levels of TMAO have been associated with an increased risk of atherosclerosis and other cardiovascular conditions, making FMO3 a potential target for therapeutic intervention.

Also see

• Trimethylaminuria
• Xenobiotic metabolism
• Flavin-containing monooxygenase
• Drug metabolism

References

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