The role of FMO3 in metabolic diseases

Abstract

Flavin containing monooxygenase 3 (FMO3) is a member of the flavin monooxygenase family, which can oxidize the precursor Trimethylamine (TMA) provided from food to produce Trimethylamine N-oxide (TMAO). The autosomal recessive inherited disease caused by partial functional loss of Fmo3 gene, which leads to excessive excretion of TMA in body fluids and emits fishy odor, is called Fish Odor Syndrome or Trimethylaminuria. This disease has been documented for 3,000 years ago and was first reported in the case report in 1970. FMO3 mainly exists in the liver and can participate in the TMA-TMAO metabolic balance in intestinal microorganisms, liver, and kidneys, closely related to insulin resistance, diabetes, cholesterol metabolism, and cardiovascular disease. Due to its wide range of catalytic substrates and low susceptibility to metabolite accumulation, its role in drug metabolism, new drug development, and discovery of new drug targets are increasingly valued. This review will summarize the research progress on the metabolic process and localization of FMO3, congenital genetic defects, metabolic diseases, and its related possible mechanisms.