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Title
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Kinetic study of neuropeptide Y (NPY) proteolysis in blood and identification of NPY$_{3-35}: a new peptide generated by plasma kallikrein
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Author
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Abstract
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| There is little information on how neuropeptide Y (NPY) proteolysis by peptidases occurs in serum, in part because reliable techniques are lacking to distinguish different NPY immunoreactive forms and also because the factors affecting the expression of these enzymes have been poorly studied. In the present study, LC-MS/MS was used to identify and quantify NPY fragments resulting from peptidolytic cleavage of NPY136 upon incubation with human serum. Kinetic studies indicated that NPY136 is rapidly cleaved in serum into 3 main fragments with the following order of efficacy: NPY336 ≫ NPY335 > NPY236. Trace amounts of additional NPY forms were identified by accurate mass spectrometry. Specific inhibitors of dipeptidyl peptidase IV, kallikrein, and aminopeptidase P prevented the production of NPY336, NPY335, and NPY236, respectively. Plasma kallikrein at physiological concentrations converted NPY336 into NPY335. Receptor binding assays revealed that NPY335 is unable to bind to NPY Y1, Y2, and Y5 receptors; thus NPY335 may represent the major metabolic clearance product of the Y2/Y5 agonist, NPY336. |
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Language
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English
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Source (journal)
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Journal of biological chemistry. - Baltimore, Md
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Publication
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Baltimore, Md
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2009
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ISSN
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0021-9258
[print]
1083-351X
[online]
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DOI
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10.1074/JBC.M109.035253
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Volume/pages
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284
:37
(2009)
, p. 24715-24724
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ISI
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000269734000006
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Full text (Publisher's DOI)
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