Lavietes B B, Regan D H, Demopoulos H B
Proc Natl Acad Sci U S A. 1974 Oct;71(10):3993-7. doi: 10.1073/pnas.71.10.3993.
L-Asparaginase (EC 3.5.1.1) inhibited respiration in sensitive, but not resistant, lines of murine lymphoma 6C3HED. Glucose, in these tumor lines, was principally converted to lactate, and very little was oxidized in the citric acid cycle or hexose monophosphate shunt. The cells derived 70-80% of their respiratory CO(2) from glutamine or glutamate. Asparaginase had no effect on the pattern of glucose utilization. The differential effect on oxygen consumption may result from the absence of asparagine synthetase in sensitive cells. Respiration may be inhibited by accumulation of the aspartate, the product of glutamate oxidation. Resistant lymphoma cells remove aspartate by converting it to asparagine. Sensitive cells, which lack asparagine synthetase, cannot make asparagine.
L-天冬酰胺酶（EC 3.5.1.1）抑制了小鼠淋巴瘤6C3HED敏感细胞系的呼吸作用，但对耐药细胞系没有影响。在这些肿瘤细胞系中，葡萄糖主要转化为乳酸，很少在柠檬酸循环或磷酸戊糖途径中被氧化。细胞呼吸产生的二氧化碳中70%-80%来自谷氨酰胺或谷氨酸。天冬酰胺酶对葡萄糖的利用模式没有影响。对氧气消耗的差异影响可能是由于敏感细胞中缺乏天冬酰胺合成酶。谷氨酸氧化产物天冬氨酸的积累可能会抑制呼吸作用。耐药淋巴瘤细胞通过将天冬氨酸转化为天冬酰胺来清除它。缺乏天冬酰胺合成酶的敏感细胞无法合成天冬酰胺。
