Open AccessCarbon sources and pathways for citrate secreted by human prostate cancer cells determined by NMR tracing and metabolic modeling
Author(s) -
Frits H. A. van Heijster,
Vincent Breukels,
Kees Jansen,
Jack A. Schalken,
Arend Heerschap
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2024357119
Subject(s) - citric acid cycle , lncap , biochemistry , citrate synthase , extracellular , glutamine , metabolism , tricarboxylic acid , metabolic pathway , biology , chemistry , cancer cell , enzyme , amino acid , cancer , genetics
Significance The human prostate accumulates high luminal citrate levels to serve sperm viability. There is only indirect qualitative evidence about metabolic pathways and carbon sources maintaining these levels. Human citrate-secreting prostate cancer cells were supplied with13 C-labeled substrates, and NMR spectra of extracellular fluid were recorded. We report absolute citrate production rates of prostate cells and direct evidence that glucose is the main carbon source for secreted citrate. Pyruvate carboxylase provides sufficient anaplerotic carbons to support citrate secretion. Glutamine carbons exchange with carbons for secreted citrate but are likely not involved in its net synthesis. Moreover, we developed metabolic models employing the13 C distribution in extracellular citrate as input to assess intracellular pathways followed by carbons toward citrate.