STUDIES ON FOLIC ACID AND VITAMIN A

二氢叶酸还原酶是几种重要药物的作用部位 广泛用于多种恶性肿瘤的化学治疗， 某些细菌感染，牛皮癣，关节炎和其他人类 疾病 了解这种酶的详细作用机制 以及这些药物对其的抑制作用， 应该有助于药物设计和化疗的合理方法。 因此，我们继续我们的研究的分离和表征， 来自各种动物的肝二氢叶酸还原酶（DHFR），即，鸡肉， 牛肉、猪肉、羊肉，与合理化，比较 研究了一种酶所表现出的看似独特的特征， 特定的动物物种可能会导致整体的合成， 了解这种不寻常的酶的一般性质。 比如说， 甲氨蝶呤的逐步谷氨酰化降低了对 羊肝DHFR，直到有六个残基的聚谷氨酸衍生物， 1/3是原来的药物。 另一方面，如果 二氢叶酸的六谷氨酸衍生物用作底物， MTX的相应六谷氨酸盐的活性现在比MTX的相应六谷氨酸盐的活性高2-5倍。 单谷氨酸盐。 因此，抑制剂以及抑制剂的Glu链长度都是相同的。 底物在体内测定DHFR抑制中可能是重要的。 最近的推测认为，类胡萝卜素的饮食摄入量可能是一个因素， 在预防人类癌症方面的作用， 类胡萝卜素营养和代谢。 作为研究的一部分， 关于正常人类胡萝卜素代谢的详细信息， 开发了一种快速分析血浆类胡萝卜素的方法。 这 HPLC程序显示了lexanthin和玉米黄质，隐黄质，番茄红素， α-和β-胡萝卜素作为主要化合物，加上两个未识别的峰。 该方法已用于测量个体对以下物质的血浆反应： 标准剂量的口服胡萝卜素， 类胡萝卜素模式。

Dihydrofolate reductase is the site of action of several important drugs widely used in the chemotherapeutic treatment of numerous malignancies, certain bacterial infections, psoriasis, arthritis and other human diseases. Understanding the detailed mechanism of action of this enzyme and its inhibition by these drugs as well as its unique molecular biology should facilitate a rational approach to drug design and chemotherapy. Thus we continue our studies on the isolation and characterization of hepatic dihydrofolate reductase (DHFR) from various animals, i.e., chicken, beef, pork, sheep, with the rationalization that the comparative investigation of a seemingly unique feature exhibited by an enzyme from a particular animal species might lead to an overall synthesis of understanding of the general nature of this unusual enzyme. For example, the stepwise glutamylation of methotrexate decreased the inhibition of sheep liver DHFR until the polyglutamate derivative with six residues was 1/3 as effective as the original drug. On the other hand, if the hexaglutamate derivative of dihydrofolate is used as substrate, the corresponding hexaglutamate of MTX is now 2-5 fold more active than the monoglutamate. Thus the Glu chain length of both the inhibitor as well as the substrate could be important in determining DHFR inhibition in vivo. Recent speculation that the dietary intake of carotenoids may be a factor in the prevention of human cancer has stimulated a renewed interest in carotenoid nutrition and metabolism. As part of a study to obtain more detailed information on carotenoid metabolims in normal humans, we have developed a rapid procedure for the analysis of plasma carotenoids. This HPLC procedure revealed leutin and zeaxanthin, cryptoxanthin, lycopene, Alpha- and Beta-carotene as major compounds plus two unidentified peaks. The method has been used in measuring the plasma response of individuals to a standard dose of oral carotene and following long term changes in plasma carotenoid patterns.