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Prominent Glutamine Oxidation Activity in Mitochondria of Hematopoietic Tumors¹

Departments of Medicine [W. H. A-K., A. A. Y., S. A-K.] and Biochemistry [A. A. Y.], University of Miami School of Medicine, Miami, Florida 33101

Well-coupled mitochondria of hematopoietic tumors were isolated from mouse erythroleukemia and rat chloroma tumors grown in male DBA/2J mice and Long-Evans rats, respectively. We used erythroleukemia and chloroma mitochondria to determine their ability to utilize glutamine as an energy source for adenosine triphosphate formation. Oxypolarographic tests showed the following. (a) Presence of a prominent glutaminase activity in erythroleukemia and chloroma mitochondria is evidenced by their active glutamine-supported respiratory state 3. (b) Glutamine oxidation is mediated through a nicotinamide adenine dinucleotide-linked reaction inhibited by rotenone. (c) Under similar conditions, mitochondria isolated from rabbit bone marrow have shown a feeble glutamine oxidation activity, while in mitochondria from rat liver the activity was not detectable and in those from rat kidney it was prominent as expected. (d) The determination of apparent K_m and V_max values for substrate-supported adenosine triphosphate formation has shown 8- to 10-fold lower K_m values for glutamine oxidation as compared to that of glutamate, with virtually the same V_max for each substrate in each mitochondria. These results clearly show the presence of a high glutamine oxidation activity in erythroleukemia and chloroma mitochondria and suggest that one of the glutamine hydrolysis products in those mitochondria may have an important role in supplying adenosine triphosphate in the corresponding malignant cells.

¹ Supported in part by USPHS Grant AM 26218 and a gift in memory of Mrs. Dolores Lourcey.

² To whom requests for reprints should be addressed at Department of Medicine (R-38), University of Miami School of Medicine, P. O. Box 016960, Miami, Fla. 33101.

Received 7/20/82. Accepted 1/27/83.