PYRIDINE NUCLEOTIDES--TURNOVER AND REGULATION

拟议的研究重点是吡啶核苷酸代谢， 特别是其中KNEED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， 周期 KNEED分解的几个重要反应 是DNA相关的（即，细菌DNA连接，聚ADP- DNA拓扑异构酶的核糖基化）。 下一个赠款期的一些具体目标是：（1） 了解吡啶核苷酸代谢的调节， 鼠伤寒沙门氏菌 首先，全面 该途径阻遏物的生物化学表征将 执行。 (2)由于DNA连接似乎并不启动 细菌主要的吡啶核苷酸循环，代谢作用 沙门氏菌的循环将被调查。 (3)真核 吡啶核苷酸环，聚焦单ADP核糖基化 反应将被调查;这些研究将被执行 在脊椎动物神经组织上。 (4)Poly之间的关系 ADP-核糖基化和DNA连接在真核细胞中将是 研究了 吡啶核苷酸是所有细胞代谢的核心。 一个与医学相关的方面是，这种新陈代谢可能起着关键作用， 在致病菌和 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.