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 recessi...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.展开更多
Background:Most duck eggs possess a fishy odor,indicating that ducks generally exhibit impaired trimethylamine(TMA)metabolism.TMA accumulation is responsible for this unpleasant odor,and TMA metabolism plays an essen-...Background:Most duck eggs possess a fishy odor,indicating that ducks generally exhibit impaired trimethylamine(TMA)metabolism.TMA accumulation is responsible for this unpleasant odor,and TMA metabolism plays an essen-tial role in trimethylaminuria(TMAU),also known as fish odor syndrome.In this study,we focused on the unusual TMA metabolism mechanism in ducks,and further explored the unclear reasons leading to the debilitating TMA metabolism.Methods:To achieve this,transcriptome,proteome,and metagenome analyses were first integrated based on the constructed duck populations with high and low TMA metabolism abilities.Additionally,further experiments were conducted to validate the hypothesis regarding the limited flavin-containing monooxygenase 3(FMO3)metabolism ability of ducks.Results:The study demonstrated that liver FMO3 and cecal microbes,including Akkermansia and Mucispirillum,par-ticipated in TMA metabolism in ducks.The limited oxidation ability of FMO3 explains the weakening of TMA metabo-lism in ducks.Nevertheless,it decreases lipid deposition and increases antibacterial activity,contributing to its survival and reproduction during the evolutionary adaptation process.Conclusions:This study demonstrated the function of FMO3 and intestinal microbes in regulating TMA metabolism and illustrated the biological significance of FMO3 impairment in ducks.展开更多
基金supported by the Youth Project Supported by Basic Scientific Research Fund of Human Provincial Education Department(Grant No.JYTQN202351)the Innovation Support Plan for Young and Middle-aged People of Shenyang City(Grant No.RC210460)+1 种基金the Medical and Industrial Cross-Project of Natural Science Foundation of Liaoning Province(Grant No.2022-YGJC-24)the Doctoral Research Initiation Fund Project of Liaoning Province(Grant No.2021-BS-206).
文摘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.
基金supported by the National Natural Science Foundation of China(31672408)the China Agriculture Research Systems(CARS-40)+1 种基金the National Key Research and Development Program of China(2021YFD1200803)the Program for Changjiang Scholars and Innovative Research Team in University(IRT_15R62).
文摘Background:Most duck eggs possess a fishy odor,indicating that ducks generally exhibit impaired trimethylamine(TMA)metabolism.TMA accumulation is responsible for this unpleasant odor,and TMA metabolism plays an essen-tial role in trimethylaminuria(TMAU),also known as fish odor syndrome.In this study,we focused on the unusual TMA metabolism mechanism in ducks,and further explored the unclear reasons leading to the debilitating TMA metabolism.Methods:To achieve this,transcriptome,proteome,and metagenome analyses were first integrated based on the constructed duck populations with high and low TMA metabolism abilities.Additionally,further experiments were conducted to validate the hypothesis regarding the limited flavin-containing monooxygenase 3(FMO3)metabolism ability of ducks.Results:The study demonstrated that liver FMO3 and cecal microbes,including Akkermansia and Mucispirillum,par-ticipated in TMA metabolism in ducks.The limited oxidation ability of FMO3 explains the weakening of TMA metabo-lism in ducks.Nevertheless,it decreases lipid deposition and increases antibacterial activity,contributing to its survival and reproduction during the evolutionary adaptation process.Conclusions:This study demonstrated the function of FMO3 and intestinal microbes in regulating TMA metabolism and illustrated the biological significance of FMO3 impairment in ducks.
