Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass.

Science
Authors
Keywords
Abstract

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.

Year of Publication
2017
Journal
Science
Volume
358
Issue
6365
Pages
941-946
Date Published
2017 11 17
ISSN
1095-9203
DOI
10.1126/science.aam9305
PubMed ID
29025995
PubMed Central ID
PMC5748897
Links
Grant list
P30 DK040561 / DK / NIDDK NIH HHS / United States
R01 CA213062 / CA / NCI NIH HHS / United States