title: 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.
authors.affiliation: Sanford|Burnham Medical Research Institute, La Jolla, California, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: De Ingeniis
authors.forename: Boris
authors.initials: B
authors.lastname: Ratnikov
authors.forename: Adam D
authors.initials: AD
authors.lastname: Richardson
authors.forename: David A
authors.initials: DA
authors.lastname: Scott
authors.forename: Pedro
authors.initials: P
authors.lastname: Aza-Blanc
authors.forename: Surya K
authors.initials: SK
authors.lastname: De
authors.forename: Marat
authors.initials: M
authors.lastname: Kazanov
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
authors.forename: Ze'ev
authors.initials: Z
authors.lastname: Ronai
authors.forename: Andrei L
authors.initials: AL
authors.lastname: Osterman
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Smith
mesh_terms: D053898:Biosynthetic Pathways / Q000502:physiology; D045744:Cell Line, Tumor; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D011392:Proline / Q000096:biosynthesis* / Q000737:chemistry; D021381:Protein Transport; D011762:Pyrroline Carboxylate Reductases / Q000378:metabolism; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase
chemical_list: D011392:Proline; D011762:Pyrroline Carboxylate Reductases; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase