کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8347766 | 1541701 | 2016 | 38 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Metabolism of peptide YY 3-36 in Göttingen mini-pig and rhesus monkey
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کلمات کلیدی
ppmTFANPYDPP-IVAUC - AUCLC–MS - LC-MSm/z - m / zTrifluoroacetic acid - اسید Trifluoroaceticdipeptidyl peptidase 4 - دیپپتیدیل پپتیداز 4In vivo metabolism - سوخت و ساز بدن in vivocharge - شارژLiquid chromatography mass spectrometry - طیف سنجی جرمی کروماتوگرافی مایعparts per million - قطعات در میلیونarea under the curve - منطقه تحت منحنیEIC - مهندسانMass-to-charge ratio - نسبت جرم به شارژPancreatic polypeptide - پالپپتید پانکراسextracted ion chromatogram - کروماتوگرافی یون استخراج شدهNeuropeptide Y - یوروپروتئین Y
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Peptide YY 3-36-amide (PYY3-36) is a peptide hormone, which is known to decrease appetite and food-intake by activation of the Y2 receptor. The current studies were designed to identify the metabolites of PYY3-36 in mini-pig and rhesus monkey. Plasma samples were analyzed by high resolution LC-MS (and MS/MS) in order to unambiguously identify the metabolites of PYY3-36. In summary, the metabolism of PYY3-36 was similar in mini-pig and rhesus monkey. Several metabolites were identified and PYY3-34 was identified at the highest levels in plasma. In addition, mini-pigs were also dosed with PYY1-36-amide, PYY3-35, PYY3-34 and [N-methyl 34Q]-PYY3-36-amide in order to investigate the mechanisms by which PYY was metabolized. PYY3-35 was rapidly converted to PYY3-34 whereas dosing of PYY3-34 to mini-pigs only showed circulating degradation products at low levels, i.e., PYY3-34 was metabolically more stable than PYY3-36 and PYY3-35. [N-methyl 34Q]-PYY3-36-amide was hypothesized to be stable toward cleavage between 34Q and 35R and after i.v. administration to mini-pigs, one major cleavage product was identified as [N-methyl 34Q]-PYY3-35. Overall, this showed that cleavage between 35R and 36Y was possible as well as between 34Q and 35R (as shown for PYY3-35), which indicated that metabolism of PYY3-36 to PYY3-34 may be a two-step process. PYY1-36 was also dosed to mini-pigs, which showed that PYY1-36 was metabolized in the C-terminal as PYY3-36. The overall degradation pattern of PYY1-36 was more complex due to the simultaneous enzymatic degradation in the N-terminal to form PYY2-34/36 and PYY3-34/36. In vitro incubations with heparin stabilized plasma showed that PYY3-36 was degraded with a half-life of 175Â min, whereas incubations with PYY3-35 (half-life of 6Â min) showed a rapid formation of PYY3-34. In conclusion, the present studies showed that PYY3-36 underwent enzymatic degradation in the C-terminal part and that the major circulating metabolite was PYY3-34. Furthermore, it may be a sequential two-step process leading to the formation of PYY3-35 and subsequently the metabolically more stable PYY3-34.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 78, April 2016, Pages 59-67
Journal: Peptides - Volume 78, April 2016, Pages 59-67
نویسندگان
Jørgen Olsen, Jacob Kofoed, Søren Ãstergaard, Birgitte S. Wulff, Flemming S. Nielsen, Rasmus Jorgensen,