Abou-Khalil W H, Yunis A A, Abou-Khalil S
Cancer Res. 1983 May;43(5):1990-3.
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 Km and Vmax values for substrate-supported adenosine triphosphate formation has shown 8- to 10-fold lower Km values for glutamine oxidation as compared to that of glutamate, with virtually the same Vmax 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.
分别从在雄性DBA/2J小鼠和Long-Evans大鼠体内生长的小鼠红白血病和大鼠绿色瘤肿瘤中分离出耦合良好的造血肿瘤线粒体。我们使用红白血病和绿色瘤线粒体来确定它们利用谷氨酰胺作为三磷酸腺苷形成能量来源的能力。极谱氧测试结果如下:(a) 红白血病和绿色瘤线粒体中存在显著的谷氨酰胺酶活性,这可通过它们活跃的谷氨酰胺支持的呼吸状态3得到证明。(b) 谷氨酰胺氧化通过一种受鱼藤酮抑制的烟酰胺腺嘌呤二核苷酸连接反应介导。(c) 在类似条件下,从兔骨髓分离的线粒体显示出微弱的谷氨酰胺氧化活性,而大鼠肝脏线粒体中未检测到该活性,大鼠肾脏线粒体中的活性如预期般显著。(d) 对底物支持的三磷酸腺苷形成的表观Km和Vmax值的测定表明,与谷氨酸相比,谷氨酰胺氧化的Km值低8至10倍,每个线粒体中每种底物的Vmax实际上相同。这些结果清楚地表明红白血病和绿色瘤线粒体中存在高谷氨酰胺氧化活性,并表明这些线粒体中谷氨酰胺水解产物之一可能在相应恶性细胞中供应三磷酸腺苷方面发挥重要作用。