Functional Specialization in Proline Biosynthesis of Melanoma

Jessica de Ingeniis, Boris Ratnikov, Adam D. Richardson, David A. Scott, Pedro Aza-Blanc, Surya K. De, Marat Kazanov, Maurizio Pellecchia, Ze'ev Ronai, Andrei L. Osterman, Jeffrey W. Smith

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92 Scopus citations


Proline metabolism is linked to hyperprolinemia, schizophrenia, cutis laxa, and cancer. In the latter case, tumor cells tend to rely on proline biosynthesis rather than salvage. Proline is synthesized from either glutamate or ornithine; both are converted to pyrroline-5-carboxylate (P5C), and then to proline via pyrroline-5-carboxylate reductases (PYCRs). Here, the role of three isozymic versions of PYCR was addressed in human melanoma cells by tracking the fate of 13C-labeled precursors. Based on these studies we conclude that PYCR1 and PYCR2, which are localized in the mitochondria, are primarily involved in conversion of glutamate to proline. PYCRL, localized in the cytosol, is exclusively linked to the conversion of ornithine to proline. This analysis provides the first clarification of the role of PYCRs to proline biosynthesis.

Original languageEnglish
Article numbere45190
JournalPLoS ONE
Issue number9
StatePublished - 14 Sep 2012
Externally publishedYes


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