Reduced folate carrier: tissue distribution and effects of chronic ethanol intake in the micropig.
BACKGROUND
Folate deficiency is common in alcoholic patients, in part due to abnormal transport across membranes relevant to folate homeostasis. The reduced folate carrier (RFC) transports monoglutamyl folates across tissue membranes and could be affected by chronic exposure to ethanol. The micropig model is suitable to study the effect of alcoholism on RFC and folate transport across membranes.


METHODS
The membrane transport of [3H]-folic acid was measured by a vacuum filtration method in jejunal brush border (JBB), liver plasma membrane (LPM), and kidney brush border (KBB) membranes vesicles from micropigs fed control or 40% ethanol diets for 12 months. RFC transcripts were analyzed by reverse transcription polymerase chain reaction in jejunal mucosa, liver, and kidney from the same animals.


RESULTS
When we compared results from three relevant membranes in control animals, the transport of [3H]-folic acid was highest in LPM, 3-fold lower in KBB (p < 0.001), and 6-fold lower in JBB (p < 0.001). The concentration of RFC transcripts per total RNA was greatest in liver, followed by kidney and jejunum. The transport of [3H]-folic acid by JBB vesicles from chronic ethanol-fed animals exhibited 2-fold lower Km and Vmax (p < 0.05), whereas there was no ethanol effect on the Vmax of [3H]-folic acid transport by LPM or KBB. RFC transcript levels were 10-fold lower in jejunal mucosa from ethanol-fed animals than in control-fed animals (p < 0.005).


CONCLUSIONS
Although our findings demonstrate different RFC transcript amounts and transport efficiencies among tissues, the present studies suggest that chronic ethanol exposure decreases the intestinal absorption of folic acid by altering the expression of RFC and consequently its transport kinetics in JBB. These findings provide a mechanism for the clinical finding of reduced folic acid absorption in chronic alcoholics.
Villanueva
J A
JA
Department of Internal Medicine, University of California, Davis 95616, USA.
Devlin
A M
AM
Halsted
C H
CH
D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005492:Folic Acid / Q000187:drug effects* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D058978:Reduced Folate Carrier Protein; D013552:Swine; D013556:Swine, Miniature
D002352:Carrier Proteins; D002492:Central Nervous System Depressants; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D058978:Reduced Folate Carrier Protein; D000431:Ethanol; D005492:Folic Acid