ABSORPTION OF MONOGLUTAMYL AND POLYGLUTAMYL FOLATES

叶酸缺乏症是营养性贫血的主要原因， 维生素营养不良 这项研究的目的是继续调查 叶酸吸收和利用的机制，并评估 孕妇叶酸缺乏症，肠道疾病患者， 酗酒者、恶性肿瘤患者和药物患者。 拟采用技术 将取决于放射性和氘的化学和生物合成 标记的单谷氨酰和多谷氨酰叶酸， 实验室 疾病患者叶酸吸收的定量检测 将基于先前报告的尿排泄技术。 分析 叶酸利用酶学将取决于酶纯化 包括亲和层析和常规方法的技术， 产品外观的色谱鉴定和动力学分析。 疾病和药物对多聚谷氨酰叶酸肠道解偶联的影响 将使用标记的合成叶酸在体内和体外进行研究， 从肠粘膜制备酶。 叶酸结合蛋白， 从运输组织如肠和肾分离，将是 用作研究叶酸/膜/药物相互作用的模型。

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.