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Differential Glutamate Metabolism in Proliferating and Quiescent Mammary Epithelial Cells.

Abstract：

:Mammary epithelial cells transition between periods of proliferation and quiescence during development, menstrual cycles, and pregnancy, and as a result of oncogenic transformation. Utilizing an organotypic 3D tissue culture model coupled with quantitative metabolomics and proteomics, we identified significant differences in glutamate utilization between proliferating and quiescent cells. Relative to quiescent cells, proliferating cells catabolized more glutamate via transaminases to couple non-essential amino acid (NEAA) synthesis to α-ketoglutarate generation and tricarboxylic acid (TCA) cycle anaplerosis. As cells transitioned to quiescence, glutamine consumption and transaminase expression were reduced, while glutamate dehydrogenase (GLUD) was induced, leading to decreased NEAA synthesis. Highly proliferative human tumors display high transaminase and low GLUD expression, suggesting that proliferating cancer cells couple glutamine consumption to NEAA synthesis to promote biosynthesis. These findings describe a competitive and partially redundant relationship between transaminases and GLUD, and they reveal how coupling of glutamate-derived carbon and nitrogen metabolism can be regulated to support cell proliferation.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Coloff JL,Murphy JP,Braun CR,Harris IS,Shelton LM,Kami K,Gygi SP,Selfors LM,Brugge JS

doi

10.1016/j.cmet.2016.03.016

subject

Has Abstract

pub_date

2016-05-10 00:00:00

pages

867-80

issue

5

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(16)30119-X

journal_volume

23

pub_type

杂志文章

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