Cancer cachexia demonstrates the energetic impact of gluconeogenesis in human metabolism
Cancer cachexia demonstrates the energetic impact of gluconeogenesis in human metabolism
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DOI：
10.1016/j.mehy.2006.04.048
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发表时间：
2006-01-01
影响因子：
4.7
通讯作者：
Wagener, D. J. Th.
中科院分区：
文献类型：
--
作者：
Bongaerts, G. P. A.;van Hatteren, H. K.;Wagener, D. J. Th.
针对癌症患者的能量流提出了基于综述的假设。该假说集中于肿瘤的缺氧条件、重要的代谢后果，尤其是糖异生、身体的适应以及癌症恶病质的发病机制。在生长的肿瘤中，O-2 浓度非常低。哺乳动物细胞需要 O-2 来有效地氧化分解糖和脂肪酸，每个葡萄糖和棕榈酸分别产生 38 和 128 个 ATP。在缺乏足够的 O-2 的情况下，它们必须切换到无氧异化，仅用 1 分子葡萄糖转化为 2 分子 ATP 和 2 分子乳酸。由于哺乳动物细胞不能发酵脂肪酸，体内肿瘤细胞完全依赖于葡萄糖发酵。因此，这些肿瘤细胞的生长需要的葡萄糖比在足够的 O-2 存在下所需的葡萄糖多约 40 倍。由于乳酸降低了细胞内 pH 值，因此降低了丙酮酸脱氢酶的活性，刺激发酵，从而放大了其自身的发酵生产。代偿性葡萄糖由乳酸的肝糖异生作用提供。然而，肝脏合成葡萄糖所需的能量必须是肿瘤细胞以无氧方式提取的能量的三倍。肝脏以氧化方式从氨基酸，尤其是脂肪酸中提取所需的能量。这可能是体重减轻的原因，即使食物摄入量似乎足够。在肝脏中，6 个 ATP 参与了 1 个葡萄糖的糖异生。这 6 个 ATP 微粒中的 4 个的能量以热量的形式耗散。这可能是癌症患者体温升高和出汗的原因。 (c) 2006 Elsevier Ltd. 保留所有权利。
A review-based hypothesis is presented on the energy flow in cancer patients. This hypothesis centres on the hypoxic condition of tumours, the essential metabolic consequences, especially the gluconeogenesis, the adaptation of the body, and the pathogenesis of cancer cachexia.In growing tumours the O-2 concentration is critically tow. Mammalian cells need O-2 for the efficient oxidative dissimilation of sugars and fatty acids, which gives 38 and 128 motes of ATP per mote glucose and palmitic acid, respectively. In the absence of sufficient O-2 they have to switch to anaerobic dissimilation, with only 2 motes of ATP and 2 motes of lactic acid from 1 mote of glucose.Since mammalian cells cannot ferment fatty acids, in vivo tumour cells completely depend on glucose fermentation. Therefore, growth of these tumour cells wilt require about 40 times more glucose than it should require in the presence of sufficient O-2.Since lactic acid lowers the intracellular pH, it decreases the activity of pyruvate dehydrogenase, stimulates fermentation, and thus amplifies its own fermentative production. Compensatory glucose is provided by hepatic gluconeogenesis from tactic acid. However, the liver must invest 3 times more energy to synthesize glucose than can be extracted by tumour cells in an anaerobic way. The liver extracts the required energy from amino acids and especially from fatty acids in an oxidative way. This may account for weight loss, even when food intake seems adequate.In the liver 6 motes of ATP are invested in the gluconeogenesis of one mote of glucose. The energy content of 4 out of these 6 motes of ATP is dissipated as heat. This may account for the elevated body temperature and sweating experience by cancer patients. (c) 2006 Elsevier Ltd. All rights reserved.