PYRIDINE NUCLEOTIDES--TURNOVER AND REGULATION

拟议的研究重点是吡啶核苷酸代谢， 特别是膝关节作为底物被消耗的反应 并且必须再生，从而产生吡啶核苷酸 周而复始。膝关节崩溃的几个重要反应 是否与DNA相关(即细菌DNA连接、聚ADP- DNA拓扑异构酶的核糖化)。 下一个授权期的一些具体目标是：(1) 了解细胞内吡啶核苷酸代谢的调节 鼠伤寒沙门氏菌。最初，一个全面的 对这一途径的抑制物的生化特征将 被执行。(2)由于DNA连接似乎不会启动 细菌中主要的吡啶核苷酸循环、代谢作用 将对沙门氏菌循环的影响进行调查。(3)真核生物 吡啶核苷酸环，聚焦于单-ADP-核糖基化 将对反应进行调查；将进行这些研究 在脊椎动物的神经元组织上。(4)聚类之间的关系 真核细胞中的ADP核糖基化和DNA连接将是 调查过了。 吡啶核苷酸是所有细胞新陈代谢的中心。 与医学相关的一个方面是，这种新陈代谢可能起着关键作用 在病原菌与细菌相互作用中的作用 吞噬细胞。

The proposed research focuses on pyridine nucleotide metabolism, particularly reactions in which KNEED is consumed as a substrate and has to be regenerated, thereby generating a pyridine nucleotide cycle. Several important reactions in which KNEED is broken down are DNA related (i.e., bacterial DNA ligation, poly ADP- ribosylation of DNA topoisomerase). Some of the specific goals for the coming grant period are, (1) to understand regulation of pyridine nucleotide metabolism in the bacterium Salmonella typhimurium. Initially, a comprehensive biochemical characterization of the repressor for this pathway will be carried out. (2) Since DNA ligation does not appear to initiate the major bacterial pyridine nucleotide cycle, the metabolic role of the Salmonella cycle will be investigated. (3) Eukaryotic pyridine nucleotide cycles, focusing mono-ADP-ribosylation reactions will be investigated; these studies will e carried out on vertebrate neuronal tissue. (4) The relationship between poly ADP-ribosylation and DNA ligation in eukaryotic cells will be investigated. Pyridine nucleotides are central to the metabolism of all cells. One medically related facet is that this metabolism may play a key role ln the interactions between pathogenic bacteria and phagocytes.