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

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.

SUBMITTER: Spinelli JB

PROVIDER: S-EPMC5748897 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Spinelli Jessica B JB Yoon Haejin H Ringel Alison E AE Jeanfavre Sarah S Clish Clary B CB Haigis Marcia C MC

Science (New York, N.Y.) 20171012 6365

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 aci ...[more]

PMID: 29025995

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