Mechanism of action of glucose and pyrimidine nucleosides on [14C]formate utilization by Ehrlich ascites cells

Abstract

• 1.

  1. When Ehrlich ascites cells are incubated in the presence of glucose, uridine, or cytidine, the intracellular concentration of free glutamate is greatly increased. The specific activity of [¹⁴C]glutamate formed from [¹⁴C]glucose is decreased 50% in the presence of 1 mM uridine.

• 2.

  2. [¹⁴C]Formate incorporation into both proteins and nucleic acids of Ehrlich ascites cells is greatly stimulated by glucose, uridine, glutamine and glutamate.

• 3.

  3. Methionine sulphoximine completely prevents the stimulations of formate utilization by glucose and uridine. These effects of methionine sulphoximine are reversed by glutamine.

• 4.

  4. It is suggested that the increased intracellular concentration of glutamate in the presence of exogenous glucose, uridine or glutamate leads to an increased availability of glutamine necessary for the synthesis of purine nucleotides and proteins. The availability of glutamate appears to be limiting for amino acid incorporation into proteins.

• 5.

  5. Exogenous [¹⁴C]glutamate is very poorly transported by Ehrlich ascites cells. After 1 h of incubation, a ratio of 0.3 for the distribution of radioactivity between cells and medium is obtained.

• 6.

  6. The incorporation of [¹⁴C]formate into free serine is stimulated 20–40-fold by glucose, uridine and cytidine. [¹⁴C]Formate incorporation into serine is greater under anaerobic conditions than under aerobic conditions.