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Functional specialization in proline biosynthesis of melanoma.

ABSTRACT: 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 (13)C-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.

SUBMITTER: De Ingeniis J

PROVIDER: S-EPMC3443215 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Functional specialization in proline biosynthesis of melanoma.

De Ingeniis Jessica J Ratnikov Boris B Richardson Adam D AD Scott David A DA Aza-Blanc Pedro P De Surya K SK Kazanov Marat M Pellecchia Maurizio M Ronai Ze'ev Z Osterman Andrei L AL Smith Jeffrey W JW

PloS one 20120914 9

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 (13)C-labeled precursors. Base ...[more]

PMID: 23024808

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