Folic acid deficiency, a major cause of nutritional anemia, is a common form of vitamin malnutrition. The goal of this research is to continue an investigation of mechanisms of folate absorption and utilization and to evaluate mechanisms of folate deficiency in pregnant women, in patients with intestinal disease, in alcoholics, in malignancy and in patients on drugs. The technology to be used will depend on chemical and biological synthesis of radioactive and deuterium labeled monoglutamyl and polyglutamyl folates by techniques developed in this laboratory. Quantitative tests of folate absorption in patients with disease will be based on urinary excretion techniques previously reported. Analysis of the enzymology of folate utilization will depend on enzyme purification techniques including affinity chromatography and conventional methods with chromatographic identification and kinetic analysis of product appearance. Effects of disease and drugs on intestinal deconjugation of polyglutamyl folates will be studied in vivo using labeled synthetic folates and in vitro using preparations of enzymes from intestinal mucosa. Folate binding proteins, isolated from transporting tissues such as intestine and kidney, will be utilized as models for study of folate/membrane/drug interactions.
