GSTDTAP  > 地球科学
DOI10.1126/science.aam9305
Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass
Spinelli, Jessica B.1,2; Yoon, Haejin1; Ringel, Alison E.1; Jeanfavre, Sarah2; Clish, Clary B.2; Haigis, Marcia C.1
2017-11-17
发表期刊SCIENCE
ISSN0036-8075
EISSN1095-9203
出版年2017
卷号358期号:6365页码:941-946
文章类型Article
语种英语
国家USA
英文摘要

Ammonia is a ubiquitous by-product of cellular metabolism; however, the biological consequences of ammonia production are not fully understood, especially in cancer. We found that ammonia is not merely a toxic waste product but is recycled into central amino acid metabolism to maximize nitrogen utilization. In our experiments, human breast cancer cells primarily assimilated ammonia through reductive amination catalyzed by glutamate dehydrogenase (GDH); secondary reactions enabled other amino acids, such as proline and aspartate, to directly acquire this nitrogen. Metabolic recycling of ammonia accelerated proliferation of breast cancer. In mice, ammonia accumulated in the tumor microenvironment and was used directly to generate amino acids through GDH activity. These data show that ammonia is not only a secreted waste product but also a fundamental nitrogen source that can support tumor biomass.


领域地球科学 ; 气候变化 ; 资源环境
收录类别SCI-E
WOS记录号WOS:000415293000051
WOS关键词UREA CYCLE ; PROLIFERATION ; BIOSYNTHESIS ; MITOCHONDRIA ; GLUTAMINASE ; SYNTHETASE
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
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文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/197354
专题地球科学
资源环境科学
气候变化
作者单位1.Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA;
2.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
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Spinelli, Jessica B.,Yoon, Haejin,Ringel, Alison E.,et al. Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass[J]. SCIENCE,2017,358(6365):941-946.
APA Spinelli, Jessica B.,Yoon, Haejin,Ringel, Alison E.,Jeanfavre, Sarah,Clish, Clary B.,&Haigis, Marcia C..(2017).Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass.SCIENCE,358(6365),941-946.
MLA Spinelli, Jessica B.,et al."Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass".SCIENCE 358.6365(2017):941-946.
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