Binding of Folic Acid to Serum Proteins

Abstract

In the serum chromatographies of healthy subjects folic acid activity (FAA) was eluted from the column in the same fractions as α₂- macroglobulin, transferrin and albumin, in this order quantitatively. Diphenylhydantoin markedly increased the binding of FAA to serum proteins, especially transferrin. A similar pronounced increase took place in myeloma, hyperthyreosis and hepatitis. In osteomyelitis the binding had decreased clearly in all protein fractions. Whenever the serum FAA had fallen below 3.0 ng/ml, all activity was bound to serum proteins. The chromatographic aberrations in FAA distribution following various pathological conditions, were seen mainly in the transferrin and α₂-macroglobulin area. No conclusions can as yet be drawn on the basis of the present study concerning the specificity of these aberrations

Demonstration of high-affinity folate binding activity associated with the brush border membranes of rat kidney.

“…Conditions for incubations and assays were as described except that the final volume of incubation was 5 ml instead of 1 ml. DISCUSSION The folate binding activity identified here in rat kidney homogenates resembles in many of its properties the soluble folate binders previously reported in milk (5,14,15), plasma (6)(7)(8)(9), and cell cytoplasm from leukocytes (26) and hog kidney (11). These properties are clearly not those of dihydrofolate reductase: the observed affinity for folic acid is much too high (Fig.…”

“…Dihydrofolate reductase has been proposed as the binding protein because this enzyme is present in relative abundance in this tissue. An alternate possibility is that this cellular factor is a high-affinity binding protein of the type that has been recently identified in milk (5), blood serum (6)(7)(8)(9), and various other tissues including the soluble fraction of porcine kidney homogenates (10)(11)(12)(13). Such proteins are characterized by rapid association and slow dissociation with folic acid (Kb = 10-1o-10-11 M), a preference for folate mono-and polyglutamates over those with one carbon substitution at the 5 position or methotrexate (7), and different effects of pH on binding of folic acid and N5-methyltetrahydrofolate (14,15 (17).…”