Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using an antiserum directed against the highly-conserved C-terminal hexapeptide amide of mammalian pancreatic polypeptide (PP), numerous immunoreactive endocrine cells were identified within the pancreas of the European common frog, R. temporaria. An acidified ethanolic extract of pancreatic tissue (0.859 g, n = 35) contained 26.2 nmol equivalents/g of tissue. Gel permeation chromatography of the extract resolved a single peak of immunoreactivity co-eluting with synthetic bovine PP standard. Reverse phase HPLC of this material resolved a single peak of immunoreactivity which was purified to homogeneity following chromatography on a semipreparative C-18 column and an analytical C-8 column. Plasma desorption mass spectrometry (PDMS) of the purified peptide resolved a single component with a molecular mass of 4240.9 Da. Direct gas phase sequencing established the sequence of the first 26 residues. Following incubation of the peptide with endopeptidase Asp-N and direct application of the digest to the sequencer, the entire primary structure of the peptide was established as: APSEPHHPGDQATQDQLAQYYSDLYQYITFVTRPRF. The derived molecular mass of this peptide, incorporating a C-terminal amide, was 4240.6 Da which is entirely consistent with that obtained by PDMS.
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PMID:The complete primary structure of pancreatic polypeptide from the European common frog, Rana temporaria. 209 Oct 68

Post-secretory metabolism is an important event in the overall homeostasis of regulatory peptides and the enzymes involved in these processes may be suitable targets for pharmacological intervention. Some examples are reviewed here. Peptide YY and neuropeptide Y, both members of the pancreatic polypeptide family, can be processed by dipeptidyl peptidase IV to their (3-36) fragments by removal of the N-terminal Tyr-Pro dipeptide, which generates a metabolite of different receptor selectivity. Aminopeptidase P and endopeptidase-24.11 also metabolize these peptides and the relative levels of these three cell-surface enzymes may regulate their interconversion between receptor-selective forms and inactive metabolites.
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PMID:Post-secretory processing of regulatory peptides: the pancreatic polypeptide family as a model example. 781 36

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 Pro2-Ile3 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 Asn29-Leu30 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.
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PMID:Processing and metabolism of peptide-YY: pivotal roles of dipeptidylpeptidase-IV, aminopeptidase-P, and endopeptidase-24.11. 790 71

Pancreatic polypeptide (PP) is a gut hormone that acts on Y4 receptors to reduce appetite. Obese humans display a reduced postprandial increase in PP and remain fully sensitive to the anorectic effects of exogenous PP. The utility of PP as an anti-obesity treatment is limited by its short circulating half-life. Insight into the mechanisms by which PP is degraded could aid in the design of long-acting PP analogs. We investigated the role of peptidases in PP degradation to determine whether inhibition of these enzymes enhanced PP plasma levels and bioactivity in vivo. Dipeptidyl peptidase IV (DPPIV) and neprilysin (NEP) were two peptidase found to cleave PP. Limiting the effect of both peptidases improved the in vivo anorectic effect of PP and PP-based analogs. These findings suggest that inhibiting the degradation of PP using specific inhibitors and/or the design of analogs resistant to cleavage by DPPIV and NEP might be useful in the development of PP as an anti-obesity pharmacotherapy.
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PMID:Degradation Paradigm of the Gut Hormone, Pancreatic Polypeptide, by Hepatic and Renal Peptidases. 2857 31