DEPRESSION OF HEPATIC FLAVIN-CONTAIING MONOOXYGENASE(FMO3) IN PATIENTS WITH LIVER CIRRHOSIS AND CANCER(ACQUIRED TRIMETHYLAMINURIA) IS CAUSED BY OVERPRODUCTION OF NITRIC OXIDE

초록

Physiologically, hepatic flavin-containing monooxygenase(FMO3)oxidizes trimethylamine(TMA),a volatile and fish-smelling metabolite arising from choline-derived nutrients,to its water-soluble and odor-less trimethylamine N-oxide which is readily excrected in urine.In those born with defect on FMO3 gene,due to diminished or absent FMO activity, a metabolic disorder called trimethylaminuria(TAMU),also known as Fish Odor Syndrome appears. In addition to TMA,many clinically useful drugs are oxidized by FMO and the patients with severe liver diseases like chronic hepatitis,cirrhosis or cancer are known to have fish odor(acquried trimethylaminuria)and their hepatic drug metabolism function have been demonstrated to be depressed.Thus, based on our previous observation indicating that the overproduced NO under a sepatic condition inhibits the expression of FMO(Park et al,1999), the overproduced NO in cirrhotic liver disease may suppress the expression of FMO3 and lead to acquired TMAU.