Functional Specialization in Proline Biosynthesis of Melanoma

被引：123
作者：
De Ingeniis, Jessica [1 ]
Ratnikov, Boris [1 ]
Richardson, Adam D. [1 ]
Scott, David A. [1 ]
Aza-Blanc, Pedro [1 ]
De, Surya K. [1 ]
Kazanov, Marat [1 ]
Pellecchia, Maurizio [1 ]
Ronai, Ze'ev [1 ]
Osterman, Andrei L. [1 ]
Smith, Jeffrey W. [1 ]
机构：
[1] Sanford Burnham Med Res Inst, La Jolla, CA USA
来源：
PLOS ONE | 2012年 / 7卷 / 09期
基金：
美国国家卫生研究院;
关键词：
CRYSTAL-STRUCTURE; BREAST-CANCER; OXIDASE; APOPTOSIS; METABOLISM; PYRROLINE-5-CARBOXYLATE; OVEREXPRESSION; STIMULATION; EXPRESSION; GENERATION;
D O I：
10.1371/journal.pone.0045190
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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 C-13-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.
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页数：9
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