PROCESSING AND METABOLISM OF PEPTIDE-YY - PIVOTAL ROLES OF DIPEPTIDYLPEPTIDASE-IV, AMINOPEPTIDASE-P, AND ENDOPEPTIDASE-24.11
PROCESSING AND METABOLISM OF PEPTIDE-YY - PIVOTAL ROLES OF DIPEPTIDYLPEPTIDASE-IV, AMINOPEPTIDASE-P, AND ENDOPEPTIDASE-24.11
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DOI：
10.1210/en.134.5.2088
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发表时间：
1994-05-01
期刊：
影响因子：
4.8
通讯作者：
TURNER, AJ
中科院分区：
文献类型：
--
作者：
MEDEIROS, MD;TURNER, AJ
比较了纯化的膜肽酶和来自人肾和空肠的刷状缘膜制剂对肽-YY (PYY) 的加工。二肽基肽酶-IV 在 Pro(2)-Ile(3) 键处水解 PYY，产生 PYY-(3-36)，它是 Y2 受体选择性配体。氨肽酶-P 从 PYY 中去除 N 末端酪氨酸，但完整的肽不是氨肽酶-N 的底物。肽链内切酶-24.11（中性肽链内切酶；脑啡肽酶）可有效代谢 PYY，其主要水解位点位于 Asn(29)-Leu(30) 键，这是一种失活裂解。血管紧张素转换酶不水解 PYY。在肾刷状缘膜中，磷酰胺显着 (>75%) 抑制 PYY 的水解，表明内肽酶 24.11 启动该制剂中 PYY 的水解。在空肠刷状缘膜中，磷酰胺的作用要小得多（抑制 15%），氨肽酶-P 和二肽基肽酶-IV 的作用的贡献是明显的。氨肽酶-P 和二肽基肽酶-IV 的生理底物尚未确定； PYY 是胰腺多肽折叠家族的成员，它可能很好地代表了那些细胞表面胞外酶的内源性底物。二肽基肽酶-IV 将 PYY 转化为代谢物 PYY-(3-36)，一种 Y2 受体类型的高度选择性激动剂。因此，三种膜肽酶在不同组织位置和不同细胞类型上的相对水平可能在 PYY 分泌后加工和代谢为受体选择性激动剂或无活性代谢物中发挥关键作用。
The processing of peptide-YY (PYY) by purified membrane peptidases and brush border membrane preparations from human kidney and jejunum has been compared. Dipeptidyl peptidase-IV hydrolyzes PYY at the Pro(2)-Ile(3) bond, producing PYY-(3-36), which is a Y2 receptor-selective ligand. Aminopeptidase-P removes the N-terminal tyrosine from PYY, but the intact peptide is not a substrate for aminopeptidase-N. Endopeptidase-24.11 (neutral endopeptidase; enkephalinase) metabolizes PYY efficiently, with a major site of hydrolysis at the Asn(29)-Leu(30) bond, an inactivating cleavage. Angiotensin-converting enzyme does not hydrolyze PYY. In renal brush border membranes, hydrolysis of PYY is substantially (>75%) inhibited by phosphoramidon, suggesting that endopeptidase-24.11 initiates hydrolysis of PYY in this preparation. In jejunal brush border membranes, phosphoramidon has a much smaller effect (15% inhibition), and contributions due to the actions of aminopeptidase-P and dipeptidyl peptidase-IV were evident. Few physiological substrates have yet been identified for aminopeptidase-P and dipeptidyl peptidase-IV; the pancreatic polypeptide fold family, of which PYY is a member, may well represent endogenous substrates for those cell surface ectoenzymes. Dipeptidyl peptidase-IV converts PYY to a metabolite PYY-(3-36), a highly selective agonist for the Y2 receptor type. Thus, the relative levels of the three membrane peptidases at different tissue locations and on different cell types may play a pivotal role in postsecretory processing and metabolism of PYY to receptor-selective agonists or inactive metabolites.