葡萄糖通过循环中的乳酸养TCA循环
Sheng Hui1,2, Jonathan M Ghergurovich1,3, Raphael J Morscher1,2
1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Nature
|October 19, 2017
概括
乳酸和葡萄糖是哺乳动物组织和瘤的主要燃料来源. 这项研究显示乳酸
科学领域:
- 代谢途径
- 营养使用量
- 癌症代谢
背景情况:
- 哺乳动物组织利用循环营养物质如葡萄糖作为能量.
- 在有氧条件下,葡萄糖通常通过三碳酸 (TCA) 循环完全代谢.
- 乳酸盐是无氧糖解的产物,是一种潜在的但被低估的营养来源.
研究的目的:
- 量化评估循环乳酸作为哺乳动物组织中的代谢燃料的作用.
- 研究乳酸对各种组织和瘤的TCA循环的贡献.
- 了解有关乳酸的糖解和TCA循环之间的关系.
主要方法:
- 系统检查小鼠的循环代谢物流.
- 输入注射13C标记的营养物质以追踪代谢途径.
- 在组织和瘤中进行TCA循环中间标记的定量分析.
主要成果:
- 乳酸在代谢物中表现出最高的循环流量,在食和禁食小鼠中超过葡萄糖.
- 在所有检查的组织中,13C-乳酸盐广泛标记TCA循环中间体.
- 在禁食状态下,循环中的乳酸是葡萄糖碳对组织TCA代谢的主要间接贡献者,除了大脑.
- 在肺部和胰腺瘤中,乳酸在禁食期间比葡萄糖更有助于TCA中间体.
结论:
- 乳酸是大多数哺乳动物组织和瘤中TCA循环的主要循环基质.
- 糖解和TCA循环是不结合的,乳酸作为一个关键的中间体.
- 乳酸作为燃料来源的作用在数量上很重要,需要进一步研究,特别是在癌症代谢中.
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