Enterohepatic circulation kinetics of bile active folate
derivatives and folate homeostasis in rats.
Shin, Ho-Chul, Fumiko Takakuwa, Minoru Shimoda, and Eiichi Kokue.
Department of Veterinary Medicine, Faculty of Agriculture, Tokyo
University of Agriculture and Technology, Fuchu, Tokyo 183, Japan
APStracts 2:0080R, 1995.
We examined the effect of enteric infusion of 5,10
-methylenetetrahydrofolate (5,10-CH2-H4PteGlu), tetrahydrofolate
(H4PteGlu), 10-formyltetrahydrofolate (10-HCO-H4PteGlu) and 5
-methyltetrahydrofolate (5-CH3-H4PteGlu) on the concentrations of
plasma 5-CH3-H4PteGlu in rats. The concentrations of plasma 5-CH3
-H4PteGlu rapidly decreased during continuous bile diversion, while
the initial levels of plasma 5-CH3-H4PteGlu were maintained by means
of enteric infusion of 5-CH3-H4PteGlu at a dose of 3 nmol/hr which
was approximately equal to total secretion of bile folates. Plasma 5
-CH3-H4PteGlu levels were also maintained by the infusion of 5,10-CH2
-H4PteGlu, H4PteGlu or 10-HCO-H4PteGlu at the same dose as 5-CH3
-H4PteGlu. The results indicate that folates secreted into the bile
are reabsorbed through the intestine to regulate plasma
concentrations of 5-CH3-H4PteGlu. We examined the secretion kinetics
of bile folates after the intravenous injection of 5-CH3-H4PteGlu or
folic acid (PteGlu) at 1 mg/kg of body weight. When 5-CH3-H4PteGlu
was injected, the bile secretion of folates other than 5-CH3-H4PteGlu
increased by less than 5 times the base level, while that of bile 5
-CH3-H4PteGlu markedly increased by about 30 times. When PteGlu was
given, the bile secretion of non-methylated tetrahydrofolates
markedly increased by 15-27 times, while that of 5-CH3-H4PteGlu
increased by about 7 times. The results suggest that oxidized folates
may be one of the sources for bile non-methylated tetrahydrofolates.
It is concluded that non-methylated tetrahydrofolates in bile play an
important role in folate homeostasis through enterohepatic
circulation, together with 5-CH3-H4PteGlu.
Received 18 July 1994; accepted in final form 28 February 1995.
APS Manuscript Number R383-4.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 April 1995.