As extracellular glutamine levels decline, asparagine becomes an essential amino acid Journal Article

   

Authors:	Pavlova, N. N.; Hui, S.; Ghergurovich, J. M.; Fan, J.; Intlekofer, A. M.; White, R. M.; Rabinowitz, J. D.; Thompson, C. B.; Zhang, J.
Article Title:	As extracellular glutamine levels decline, asparagine becomes an essential amino acid
Abstract:	When mammalian cells are deprived of glutamine, exogenous asparagine rescues cell survival and growth. Here we report that this rescue results from use of asparagine in protein synthesis. All mammalian cell lines tested lacked cytosolic asparaginase activity and could not utilize asparagine to produce other amino acids or biosynthetic intermediates. Instead, most glutamine-deprived cell lines are capable of sufficient glutamine synthesis to maintain essential amino acid uptake and production of glutamine-dependent biosynthetic precursors, with the exception of asparagine. While experimental introduction of cytosolic asparaginase could enhance the synthesis of glutamine and increase tricarboxylic acid cycle anaplerosis and the synthesis of nucleotide precursors, cytosolic asparaginase suppressed the growth and survival of cells in glutamine-depleted medium in vitro and severely compromised the in vivo growth of tumor xenografts. These results suggest that the lack of asparaginase activity represents an evolutionary adaptation to allow mammalian cells to survive pathophysiologic variations in extracellular glutamine. Exogenous asparagine can rescue growth and survival of glutamine-deprived cells. Pavlova et al. show that asparagine is not catabolized to produce other amino acids or biosynthetic intermediates, but rather maintains protein synthesis. Introduction of asparaginase suppressed the growth and survival of glutamine-depleted cells and compromised the growth of tumor xenografts. © 2017 Elsevier Inc.
Keywords:	asparaginase; translation; glutamine; asparagine
Journal Title:	Cell Metabolism
Volume:	27
Issue:	2
ISSN:	1550-4131
Publisher:	Elsevier Inc.
Date Published:	2018-02-06
Start Page:	428
End Page:	438.e5
Language:	English
DOI:	10.1016/j.cmet.2017.12.006
PROVIDER:	scopus
PMCID:	PMC5803449
PUBMED:	29337136
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85040368570&doi=10.1016%2fj.cmet.2017.12.006&partnerID=40&md5=854fd04ab45c6449753d4a14efcb130a
Notes:	Article -- Export Date: 3 December 2018 -- Source: Scopus

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