Board M, Newsholme E
Department of Biochemistry, University of Oxford, U.K.
Biochem Mol Biol Int. 1996 Nov;40(5):1047-56. doi: 10.1080/15216549600201683.
Metabolic fates of pyruvate (CO2, lactate, citrate) in normal and neoplastic cells have been assessed. Pyruvate consumption by tumour cells falls (by 72-85%) and mean percentage oxidation rises from 75% to 91% with hydroxycitrate. Ratios of rates of oxidation of (3-(14)C-pyruvate) : (1-(14)C-pyruvate), indicating CO2 produced from TCA cycle activity : that from PDH activity, are higher for tumorigenic (0.17-0.24) than for non-tumorigenic (0.005-0.04) cells and increase (0.27-0.65 and 0.13-0.29, respectively) with hydroxycitrate. Although maximal ATP-citrate lyase activities do not correlate with malignancy, citrate may be a major fate of glutaminolytic pyruvate in tumour cells. Citrate accounts for 14-37% of consumed glutamine compared with 11-13% being recovered as CO2. By contrast, approximately 100% of glycolytic pyruvate is converted to lactate.
已评估了正常细胞和肿瘤细胞中丙酮酸的代谢去向(二氧化碳、乳酸、柠檬酸)。肿瘤细胞对丙酮酸的消耗量下降(下降72 - 85%),使用羟基柠檬酸后平均氧化百分比从75%升至91%。(3-(14)C-丙酮酸)与(1-(14)C-丙酮酸)的氧化速率之比,即三羧酸循环活动产生的二氧化碳与丙酮酸脱氢酶活动产生的二氧化碳之比,致瘤细胞(0.17 - 0.24)高于非致瘤细胞(0.005 - 0.04),且使用羟基柠檬酸后增加(分别为0.27 - 0.65和0.13 - 0.29)。尽管最大的ATP-柠檬酸裂解酶活性与恶性程度无关,但柠檬酸可能是肿瘤细胞中谷氨酰胺分解产生的丙酮酸的主要去向。与作为二氧化碳回收的11 - 13%相比,柠檬酸占消耗的谷氨酰胺的14 - 37%。相比之下,糖酵解产生的丙酮酸约100%转化为乳酸。