cyclic-gmp and ureidosuccinic-acid

Production of cellulose, a stress response-mediated process in enterobacteria, is modulated in Escherichia coli by the activity of the two pyrimidine nucleotide biosynthetic pathways, namely, the de novo biosynthetic pathway and the salvage pathway, which relies on the environmental availability of pyrimidine nitrogenous bases. We had previously reported that prevalence of the salvage over the de novo pathway triggers cellulose production via synthesis of the second messenger c-di-GMP by the DgcQ (YedQ) diguanylate cyclase. In this work, we show that DgcQ enzymatic activity is enhanced by UTP, whilst being inhibited by N-carbamoyl-aspartate, an intermediate of the de novo pathway. Thus, direct allosteric control by these ligands allows full DgcQ activity exclusively in cells actively synthesizing pyrimidine nucleotides via the salvage pathway. Inhibition of DgcQ activity by N-carbamoyl-aspartate appears to be favoured by protein-protein interaction between DgcQ and PyrB, a subunit of aspartate transcarbamylase, which synthesizes N-carbamoyl-aspartate. Our results suggest that availability of pyrimidine bases might be sensed, somehow paradoxically, as an environmental stress by E. coli. We hypothesize that this link might have evolved since stress events, leading to extensive DNA/RNA degradation or lysis of neighbouring cells, can result in increased pyrimidine concentrations and activation of the salvage pathway.

Topics: Aspartate Carbamoyltransferase; Aspartic Acid; Biosynthetic Pathways; Cellulose; Cyclic GMP; DNA; Escherichia coli; Escherichia coli Proteins; Phosphorus-Oxygen Lyases; RNA; Uridine Triphosphate

Many roles have been suggested for N-acetyl-aspartate in brain function because of it being located almost exclusively in that organ. However, its true role remains to be demonstrated. We show here that N-acetyl-aspartate: 1) binds to a hydrophobic protein fraction from the cerebral cortex of the rat, which specifically binds L-aspartate, L-glutamate, and gamma-amino-butyric acid; and 2) has a marked inhibitory effect on the aspartate binding sites of this proteolipid fraction. Structural analogs of N-acetyl-aspartate, i.e. N-carbamyl-aspartate and N-methyl-aspartate also inhibit the L-aspartate binding by the brain protein fraction used.

Topics: Animals; Aspartic Acid; Cerebral Cortex; Cyclic AMP; Cyclic GMP; Male; N-Methylaspartate; Protein Binding; Proteolipids; Rats; Rats, Inbred Strains