Prominent glutamine oxidation activity in mitochondria of avian transplantable hepatoma induced by MC‐29 virus

Abstract

Well coupled mitochondria were isolated from transplantable chicken hepatoma induced by MC-29 virus. The mitochondrial phosphate-dependent and phosphate-independent glutaminase activities were increased compared with those from normal chicken liver. Glutamate dehydrogenase was undetectable in the tumor mitochondria. Oxypolarographic tests showed the following: glutamine oxidation was prominent in the tumor mitochondria and was mediated through an NAD-linked reaction, while mitochondria from the liver showed a feeble glutamine oxidation; glutamine oxidation by tumor mitochondria was inhibited either by aminooxyacetate, inhibitor of transaminases, or prior incubation of mitochondria with DON (6-diazo-5-oxonorleucine), which inhibited mitochondrial glutaminases. Bromofuroate, inhibitor of glutamate dehydrogenase, had little or no effect; and glutamate oxidation was also inhibited by aminooxyacetate, while it was not affected by DON. These findings clearly show a high glutamate oxidation activity in the hepatoma and indicate that the product of glutamine hydrolysis, glutamate, is catabolized via transamination in the mitochondria to supply ATP.

c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism

“…Because glutamine is a precursor for glutathione20, glutathione levels were measured by flow cytometry and were found diminished with glutamine withdrawal or RNAi mediated reduction of GLS (Figure S4 and Table S2) that is also associated with an increase in ROS levels (Figure S3c) and cell death in the P493-6 cells (Figures 2e and S5). It is notable shortly after the MYC proto-oncogene was discovered, that the MC29 retrovirus which bears the v-myc oncogene was found to enhance glutamine catabolism and mitochondrial respiration in transplantable avian liver tumor cells21. Thus, our findings functionally link historical observations with Myc, glutaminase and glutamine metabolism.…”

Improvement of CHO Cell Culture Medium Formulation: Simultaneous Substitution of Glucose and Glutamine

“…Alanine is normally obtained in cell culture as a product of the transamination reaction between pyruvate and glutamate. The reaction also produces R-ketoglutarate, and generally this is the most common way to obtain this compound in cells that are proliferating rapidly, simultaneously reducing the ammonium generation (Matsuno et al, 1994). The low alanine production that is observed for the slowly metabolizable sugars should probably be linked to the low availability of pyruvate in the cell due to the slow glycolysis.…”

Analysis of tricarboxylic acid-cycle metabolism of hepatoma cells by comparison of 14CO2 ratios

“…1). This hypothesis is supported by data indicating that glutamine oxidation is a prominent feature of many tumour preparations, including Morris hepatoma in vivo (Sauer & Dauchy, 1978), isolated Ehrlich ascites cells (Lazo, 1981) and isolated tumour mitochondria (Matsuno et al, 1986;Abou-Khalil et al, 1983). Glutamine oxidation is correlated with mitochondrial glutaminase activity in Morris hepatomas (Kovacevic & Morris, 1972).…”