Reductive Catabolism of Pyrimidine Bases by Pseudomonas Aeruginosa

Nitrogen is essential to biological processes and is present in all living systems. Thus, in nature, nitrogen plays a number of important biological roles due to its chemical properties. In fact, it is a necessary component for the synthesis of such compounds as amino acids and nucleic acids. Nitrogen starvation causes a cell to turn on every possible cellular mechanism to provide it with a nitrogen source. This includes the degradation of nitrogen rich biomolecules. Amino acids and nucleic acids are examples of nitrogen-rich biomolecules that can be utilized for cellular survival. Even though the basic building blocks of nucleic acids, such as the pyrimidine bases uracil and thymine, are involved in DNA and RNA synthesis, they can be catabolized for nitrogen. Considerably more is known about the biosynthesis of pyrimidine nucleotides than the degradation of the pyrimidine bases uracil and thymine. At least two nitrogen-providing catabolic pathways are known to exist which allow an organism to provide itself with potential nitrogen sources from pyrimidine bases. Regulation of gene expression in organisms might be anticipated to ensure their continued survival and propagation in a nitrogen-poor environment. This necessitates a highly coordinated and efficient enzymatic pathway for the catabolism of nitrogen-rich biomolecules. Optimally, the genes encoding this pathway will be coordinately regulated for the degradation of nitrogen-rich biomolecules. The synthesis of the respective catabolic pathway enzymes should occur under nitrogen-limiting conditions. These genes should not be expressed in a nitrogen rich environment so that the metabolic precursors, such as pyrimidine bases, are not wasted. Pseudomonas aeruginosa, a Gram-negative bacterium known to be a human pathogen, is used in this study. It has been shown that P. aeruginosa degraded and utilized pyrimidine bases as nitrogen sources for growth. This study of P. aeruginosa has been conducted to obtain more information about its nitrogen metabolism, its regulation of gene expression and its pathway of pyrimidine catabolism. Growth, physiological and genetic studies of P. aeruginosa strains were undertaken to complete these objectives. In the broader perspective, pyrimidine degradation investigations are highly relevant to the study of human cancer chemotherapy, to understanding pyrimidine catabolism disorders in humans and to the study of how aromatic ring structures are decomposed