Hepatic gluconeogenesis influences (13)C enrichment in lactate in human brain tumors during metabolism of [1,2-(13)C]acetate.
Hepatic gluconeogenesis influences (13)C enrichment in lactate in human brain tumors during metabolism of [1,2-(13)C]acetate.
复制标题
DOI：
10.1016/j.neuint.2016.03.015
复制
发表时间：
2016-07
影响因子：
4.2
通讯作者：
Maher EA
中科院分区：
文献类型：
--
作者：
Pichumani K;Mashimo T;Vemireddy V;Kovacs Z;Ratnakar J;Mickey B;Malloy CR;DeBerardinis RJ;Bachoo RM;Maher EA
富含13 C的化合物在人类恶性肿瘤中容易代谢。通过活组织检查或手术切除获得的肿瘤碎片可以被酸提取，并且代谢物如谷氨酸、谷氨酰胺、2-羟基戊二酸、乳酸等的13 C NMR光谱提供了关于原位肿瘤代谢的丰富信息来源。最近，我们观察到13 C-13 C自旋-自旋耦合在13 C NMR谱的乳酸从病人脑肿瘤谁是注入[1，2 - 13 C]乙酸手术前。我们发现，在4例患者中，输注13 C富集醋酸盐与血浆中可检测到的13 C富集葡萄糖的合成相关。来源于肝脏中[1，2 - 13 C]乙酸盐代谢的13 C标记葡萄糖和肿瘤中的脑丙酮酸盐再循环一起导致脑肿瘤中13 C标记乳酸盐池的产生。它们对脑肿瘤中乙酸盐代谢的综合贡献小于4.0%，显著低于肿瘤中柠檬酸循环中乙酸盐的直接氧化。
13C-enriched compounds are readily metabolized in human malignancies. Fragments of the tumor, acquired by biopsy or surgical resection, may be acid-extracted and 13C NMR spectroscopy of metabolites such as glutamate, glutamine, 2-hydroxyglutarate, lactate and others provide a rich source of information about tumor metabolism in situ. Recently we observed 13C-13C spin-spin coupling in 13C NMR spectra of lactate in brain tumors removed from patients who were infused with [1,2-13C]acetate prior to the surgery. We found, in four patients, that infusion of 13C-enriched acetate was associated with synthesis of 13C-enriched glucose, detectable in plasma. 13C labeled glucose derived from [1,2-13C]acetate metabolism in the liver and the brain pyruvate recycling in the tumor together lead to the production of the 13C labeled lactate pool in the brain tumor. Their combined contribution to acetate metabolism in the brain tumors was less than 4.0%, significantly lower than the direct oxidation of acetate in the citric acid cycle in tumors.