Hepatic uptake, intracellular accumulation and biliary secretion of 5-methyltetrahydrofolate.
Transport of the reduced folate coenzyme, 5-methyltetrahydrofolate, from plasma to bile was studied in the isolated perfused rat liver. The system was inhibited by metabolic poisons, pteroylglutamate, 10-formylfolate, and amethopterin. The coenzyme was concentrated in hepatic parenchyma 1.3 fold over the concentration in the medium. After an initial delay of approximately 20 min the biliary secretion of the coenzyme nearly paralleled the hepatic uptake, and the coenzyme was concentrated in bile 15-19 times above the perfusion medium. The transport process was saturable with a Kt value of 0.45 mM and Vmax of 0.66 mumoles/hr/g liver. Chromatography of the bile revealed minimal biotransformation of the secreted coenzyme. In experiments in vivo 5-methyltetrahydrofolate was absorbed readily from the intestine, as demonstrated by the urinary excretion of 32-40% of the dose within 48 hr after peroral administration. These studies indicate that hepatic uptake and biliary secretion of 5-methyltetrahydrofolate occurs by an energy-dependent, carrier-mediated process in which the coenzyme accumulates in the liver, is secreted into bile against a high concentration gradient and undergoes enterohepatic circulation.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001711:Biotransformation; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D013763:Tetrahydrofolates / Q000378:metabolism* / Q000652:urine
D013763:Tetrahydrofolates; C005984:5-methyltetrahydrofolate