Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50502 (Hip)
 7,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin I(AI)-converting enzyme (ACE) (EC 3.4.15.1) was solubilized from the membrane fraction of chicken lung using trypsin and nonidet P40 extraction, and then purified to homogeneity by captopril affinity chromatography. Comparison of trypsin-extracted and detergent-solubilized membrane-bound converting enzyme by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and isoelectric focusing indicated that the membrane-binding sequence contributed to a large extent to the size and charge of the enzyme. Both forms of the enzyme were glycoproteins but they differed in the glucidic content; 4.5% by weight of the enzyme in the trypsin-extracted ACE and 15% by weight of the enzyme in the detergent-solubilized ACE. In both cases hexoses were the most abundant residues. Both forms of the enzyme were found to contain 1 g-atom zinc/mol enzyme. The purified enzymes did not only split Hip-His-Leu but also AI and bradykinin. The Michaelis constant (Km) and maximum velocity (Vmax) values of the trypsin-extracted ACE for Hip-His-Leu were 52 x 10(-5) mol/l and 15.36 nmol/min respectively, and for AI they were 7.8 x 10(-5) mol/l and 0.45 nmol/min respectively. The Km and Vmax values of the detergent-solubilized ACE for Hip-His-Leu were 32 x 10(-5) mol/l and 11.75 nmol/min respectively, and for AI they were 6.5 x 10(-5) mol/l and 0.97 nmol/min.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of chicken lung angiotensin I-converting enzyme. 131 47

Three distinct peptidyldipeptidases (exopeptidases releasing carboxyl terminal dipeptide residues) can be solubilized from nerve terminal membrane fractions from whole rat brain or striatum, and separated by ion exchange chromatography. Brain angiotensin-converting enzyme (PDP-1) cleaves Hip-His-Leu, but not 80 nM [3H-Tyr1, Leu5]-enkephalin, and is markedly inhibited by several specific inhibitors such as captopril, teprotide, and MK-422. Enkephalinase (PDP-2) cleaves 80 nM [3H-Tyr1, Leu5]-enkephalin, but not Hip-His-Leu; it is not inhibited by any of the standard competitive inhibitors of angiotensin-converting enzyme (all analogs of carboxyl-terminal peptide sequences Phe-Ala-Pro or Ala-Pro), but is strongly inhibited by captopril analogs such as thiorphan (Phe-Gly analog). A third peptidyldipeptidase (PDP-3) cleaves Hip-His-Leu, but not 80 nM [3H-Tyr1, Leu5]-enkephalin; it is inhibited by dipeptide analog inhibitors such as captopril and thiorphan, but not by longer peptides such as teprotide or tripeptide analog inhibitors such as MK-422. Both PDP-2 (enkephalinase) and PDP-3 are apparently present in nerve terminal membranes predominantly as inactive proenzyme precursors, which elute from DEAE-cellulose at high salt concentration, and are activated very slowly by a process involving one or more trypsin-like enzymes. Rechromatography of activated PDP-2 and PDP-3 achieves a nearly complete separation of the two enzymes, both markedly purified, since each is much less acidic than its proenzyme precursor. Purified enkephalinase does not appear to have any significant endopeptidase activity. It cleaves Hip-Phe-Arg 200 times more effectively than Hip-Phe-Arg-NH2, and appears to be quite selective for cleaving the terminal dipeptide residue, Phe-Arg, from bradykinin, with no release of the second dipeptide and no cleavage of the Gly4-Phe5 interior peptide bond.
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PMID:Purification and characterization of enkephalinase, angiotensin converting enzyme, and a third peptidyldipeptidase from rat brain. 631 70