BIOSYNTHESIS OF VITAMIN B1 AND VITAMIN B6

值得注意的是，60年后的发现和合成， 维生素B1和维生素B6，以及对它们的营养 重要性，以及30年后，阐明其生化 功能，其生物合成的知识仍然不完整。主要 两种维生素的碳源都是葡萄糖。的路线 与大肠杆菌中的两种维生素的关系越来越清楚， 但问题依然存在另一条尚未定义的通往B1的路线运行 在酵母中。酵母中B6的途径是未知的。 本建议的两个主要目的是：（i）澄清 的步骤，导致两个维生素在酵母，和一个关键的 检查是否存在一种替代产品的问题 （二）两个人之间的关系;（三）最后澄清 两种代谢途径的几种中间体的状态 大肠杆菌中的维生素 维生素B1：使用多个13 C标记样品的掺入研究 葡萄糖和核糖将限定C1和C2单元的进入模式， 都是从核糖衍生的，转化为E中B1的嘧啶部分。杆菌和 将确定葡萄糖衍生的碳原子的精确来源， 酵母中的硫胺素。大多数所需的乘以13 C标记的样品将 因为它们在商业上不可得，所以必须合成。 维生素B6：酵母中B6的来源不明。不能假设A 先验地，酵母中的B6途径与大肠杆菌中的相同， 由于其他维生素（例如，硫胺素、烟酸）具有不同的来源模式 在原核生物和真核生物中。将回答两个问题： B6在酵母中的生物合成与E.杆菌 (ii)在酵母中，维生素B6是维生素B6的嘧啶单元的前体。 B1，正如最近所建议的那样。13 C标记的实验 基质，然后通过高场13 C NMR分析，将提供 这将有助于回答这些问题的证据。 根据定义，维生素不是在哺乳动物中合成的。现在很明显 B1和B6的主要前体是葡萄糖和其他常见的 代谢物。这项研究的长远目标是找出 在人体组织中被阻断的每个途径中的步骤，从而使 化合物维生素。

It is remarkable that 60 years after the discovery and synthesis of Vitamin B1 and of Vitamin B6, and the recognition of their nutritional importance, and 30 years after the elucidation of their biochemical function, knowledge of their biosynthesis is still incomplete. The major source of the carbons of each of the two Vitamins is glucose. The routes to the two Vitamins in a bacterium, Escherichia coli, are becoming clear, but questions remain. A different, as yet undefined, route to B1 operates in yeast. The path to B6 in yeast is unknown. The two major objectives of the present proposal are (i) the elucidation of the steps leading to the two Vitamins in yeast, and a critical examination of the question whether there exists a precursor-product relationship between the two Vitamins; and (ii) final clarification of the status of several intermediates of the metabolic routes to the two Vitamins in E.coli. Vitamin B1: Incorporation studies with multiply 13C labeled samples of glucose and ribose will define the mode of entry of a C1 and a C2 unit, both derived from ribose, into the pyrimidine moiety in B1 in E. coli, and will determine the precise origin of the glucose-derived carbon atoms of thiamin in yeast. Most of the required multiply 13C labeled samples will have to be synthesized since they are not available commercially. Vitamin B6: The origin of B6 in yeasts is unknown. It cannot be assumed a priori that the route to B6 in yeast is identical with that in E.coli, since other Vitamins (e.g., thiamin, niacin) have distinct modes of origin in prokaryotes and eukaryotes. Two questions will be answered: Is the mode of biosynthesis of B6 in yeast the same or different from that in E. coli. (ii) In yeast is Vitamin B6 a precursor of the pyrimidine unit of Vitamin B1, as has recently been suggested. Experiments with multiply 13 C-labeled substrates, followed by analysis by high field 13C NMR, will provide the evidence which will serve to answer these questions. By definition, Vitamins are not synthesized in mammals. It is now evident that the primary precursor of B1 and B6 are glucose and other common metabolites. It is the long term objective of the study to identify the step in each pathway which is blocked in human tissues, thereby making the compounds Vitamins.