Renal folate absorption and the kidney folate binding protein. I. Urinary clearance studies.
The kidney possesses a high concentration of a folate binding protein (FBP) that resides primarily in the brush-border membrane (BBM) of the proximal tubular cells. To assess the possible involvement of this protein in renal conservation of folate we determined the urinary clearance, in rats, of three forms of folates with sharply different affinities for FBP. After single intravenous injections of 0.1 to 1.0-nmol doses of radioactive folates the urinary clearance based on radioisotope determination was in the sequence: folic acid less than 5-methyltetrahydrofolate (5-CH3 THF) much less than methotrexate. At higher doses the urinary folate clearance was increased and the differences between the three injected forms were narrowed and were no longer noticeable at 100-nmol doses. Under conditions of continuous infusion to attain plasma folate levels of 2.3-5.7 pmol/ml, the urinary clearance based on chromatographic analyses of plasma and urine after correction for plasma folate binding was 0.20 ml/min for folic acid, 0.37 ml/min for 5-CH3 THF, and 1.76 ml/min for methotrexate. These chromatographic analyses have also shown the presence in both plasma and urine of metabolites formed from infused folates. Metabolites found after infusion of folic acid include 5-CH3 THF with a urinary clearance of 0.3 ml/min and an unknown with a urinary clearance of 0.8 ml/min. The latter metabolite appears also to occur in plasma and urine after infusion of 5-CH3 THF. Infusion of methotrexate was associated with the appearance of a metabolite with a urinary clearance of 2.5 ml/min. This sequence of urinary clearance is in inverse order to the affinities of these three forms of folate for the kidney BBM FBP.(ABSTRACT TRUNCATED AT 250 WORDS)