Mechanism and control of degradation and resynthesis of adenylates in tumour cells

Abstract

A comparative study revealed that Ehrlich ascites carcinoma (EAC) cells use glutamine plus inosine for regeneration of adenylates via the purine nucleotide cycle, whereas AS 30D hepatoma cells use adenosine instead. This observation can be correlated with the very low production of aspartate from glutamine in hepatoma cells. Although glucose is an important energy fuel for EAC, it cannot maintain a high enough level of adenylates unless glutamine is also present. Kinetic analysis of hydrolysis of ATP and ADP in the presence of rotenone suggests that deamination of AMP does not maintain a high enough ATP/ADP ratio and probably does not act as energy buffer after inhibition of cell respiration. It seems that, compared with normal cells, malignant cells have the ability for a very rapid regeneration of adenylates. It is proposed that instability of the adenine nucleotide pool, owing to frequent aerobic-anaerobic transitions, represents an essential feature of neoplasia, with profound impact on the whole metabolism of tumour cells.

Untreated Glioblastoma Multiforme: IncreasedMyo-inositol and Glutamine Levels in the Contralateral Cerebral Hemisphere at Proton MR Spectroscopy

“…In particular, through aspartate, glutamine is essential for the synthesis of purine and pyrimidine bases as a carbon and nitrogen donor (22). This latter phenomenon seems to be important for the adaptation of tumors to transitions from the aerobic to the anaerobic state (23,24). Furthermore, it has been hypothesized that glutamine serves as an energy fuel through glutaminolysis (25), which seems to be a prerequisite for tumor cell growth (26).…”

Control and function of the transamination pathways of glutamine oxidation in tumour cells

“…Experiments with Ehrlich ascites carcinoma (EAC) cells supported this proposal [8]. Also, it was shown that the cells of AS 30D hepatoma do not use this pathway for the resynthesis of adenylates [9], and that they have a very low rate of synthesis of aspartate. This was the reason to undertake a detailed study of the pathways of glutamine oxidation, with the question why AS 30D hepatoma compared with EAC has much lower capability for synthesis of aspartate.…”

“…The high production of aspartate in EAC can be correlated with the regeneration of the pool of adenine nucleotides via the purine nucleotide cycle. Hepatoma cells do not use the same mechanism for resynthesis of AMP [9]. This suggests that in some tumour cell lines a high activity of the aspartate aminotransferase pathway might be important for resynthesis of adenylates and, therefore, for energy status of the cells.…”