Cytosol aminopeptidase

This zinc-dependent enzyme [EC 3.4.11.1], also referred to as cytosol aminopeptidase, leucyl aminopeptidase, and peptidase S, catalyzes the hydrolysis of a terminal peptide bond such that there is a release of an N-terminal amino acid, Xaa-Xbb-, in which Xaa is preferably a leucyl residue, but may be other aminoacyl residues including prolyl (although not arginyl or lysyl). Xbb may be prolyl. In addition, amino acid amides and methyl esters are also readily hydrolyzed, but the rates with arylamides are exceedingly slow. The enzyme is activated by heavy metal ions. 

Aminopeptidase, cytosol Aminopeptidase, leucine Aminopropyltransferase, putrescine Aminotransferase Aminotransferase, alanine Aminotransferase, aspartate Aminotransferase, glutamate-glyoxylate Aminotransferase, ornithine-keto acid Aminotransferase, serine-glyoxylate Ammonia... 

EC 3.4.11.1 Cytosol aminopeptidase Aminoacyl-peptide -1- HjO amino acid+peptide - SM... 

The oligopeptide may also be sequenced from the AT-terminus by an enzymic method using the cytosol aminopeptidase of pig kidney or cattle lens. This enzyme acts on all peptide bonds except arginyl or lysyl bonds. The concentrations of identified free amino acids are measured at given time intervals. The amino acid sequence of the... 

Relative (group) specificity in which certain enzymes can act on a group of structurally similar substrates, e.g. cytosol aminopeptidase (Section 4.4). 

An exopeptidase that sequentially releases an amino acid from the N-terminus of a protein or peptide. Examples include cystinyl aminopeptidase (MEROPS M01.011), which removes a terminal cysteine from the biologically important peptides oxytocin and vasopressin, and methionyl aminopeptidase (M24.001), which removes the initiating methionine from cytosolic... 

It was clear for some time that a number of zinc enzymes required two or more metal ions for full activity, but in the absence of X-ray structural data the location of these metal centres with regard to one another was often uncertain. When the first 3-D structures began to appear, it became clear that the metals were in close proximity. A particular feature of many of these enzymes was the presence of a bridging ligand between two of the metal sites, usually an Asp residue of the protein, which is occasionally replaced by a water molecule. While some of the sites contain only Zn ions, several contain Zn in combination with Cu (in cytosolic superoxide dismutases) Fe (in purple acid phosphatases) or Mg (in alkaline phosphatase and the aminopeptidase of lens). 

Increased permeability is just one prerequisite in the development of useful peptide prodrugs. Another condition is that efficient bioactivation must follow absorption. Mucosal cell enzymes able to hydrolyze peptides include exopeptidases such as aminopeptidases and carboxypeptidases, endopepti-dases, and dipeptidases such as cytosolic nonspecific dipeptidase (EC 3.4.13.18), Pro-X dipeptidase (prolinase, EC 3.4.13.4), and X-Pro dipeptidase (prolidase, EC 3.4.13.9). For example, L-a-methyldopa-Pro was shown to be a good substrate for both the peptide transporter and prolidase. This dual affinity is not shared by all dipeptide derivatives, and, indeed, dipeptides that lack an N-terminal a-amino group are substrates for the peptide transporter but not for prolidase [29] [33] [34],... 

A novel concept of using bioadhesive polymers as enzyme inhibitors has been developed [97]. Included are derivatives of poly acrylic acid, polycarbophil, and car-bomer to protect therapeutically important proteins and peptides from proteolytic activity of enzymes, endopeptidases (trypsin and a-chymotrypsin), exopeptidases (carboxypeptidases A and B), and microsomal and cytosolic leucine aminopeptidase. However, cysteine protease (pyroglutamyl aminopeptidase) is not inhibited by polycarbophil and carbomer [97]. 

Many aminopeptidases are metalloenzymes.437 Most studied is the cytosolic leucine aminopeptidase which acts rapidly on N-terminal leucine and removes other amino acids more slowly. Each of the subunits of the hexameric enzyme contains two divalent metal ions, one of which must be Zn2+ or Co2+438/439 A methionine aminopeptidase from E. colt contains two Co2+ ions440/441 and a proline-specific aminopeptidase from the same bacterium two Mn2+.442 In all of these enzymes the metal ions are present as dimetal pairs similar to those observed in phosphatases and discussed in Section D,4 and to the Fe-Fe pairs of hemerythrin and other diiron proteins (Fig. 16-20). A hydroxide ion that bridges the metal ions may serve as the nucleophile in the aminopeptidases.438 A bound bicarbonate ion may assist.4383... 

Aminopeptidases that catalyze the hydrolysis of cysteinyl peptides are known. The membrane-bound aminopeptidases are glycoproteins, usually with molecular weights of about 100,000 daltons. They appear to be metalloproteins, one of the better known being a zinc-containing enzyme. Other enzymes, such as the leucine aminopeptidase, are cytosolic but, at least in this case, are also zinc-containing. The substrate specificity of these enzymes varies but most are relatively nonspecific. 

Many aminopeptidases are metalloenzymes. Most studied is the cytosolic leucine aminopeptidase which acts rapidly on N-terminal leucine and removes other amino acids more slowly. Each of the subunits of the hexameric enzyme contains two divalent metal ions, one of which must be Zn + or A me-... 

Proteasomes rather than cytosolic carboxy-peptidases act to trim the C-terminal amino acids to conform the peptide to the proper size for MHC class-I presentation. Presentation from N-extended precursors is inhibited by acetylation of the terminal a-amino group at the N-terminus [354], which prevents the peptide to be cleaved by aminopeptidases e.g. leucine aminopeptidase) but not by proteasomes or endopeptidases. The TAP system transports peptides to the ER including both mature epitopes and longer precursors. It seems then that the peptides to be presented by MHC class-I can arise from N-extended precursors both in the cytosol and in the endoplasmic reticulum (ER). This assertion has been experimentally confirmed [355,356]. 

These enzymes have been linked here because they have some common applications in diagnostic enzymology. Alanine aminopeptidase (AAP) and leucyl arylamidase (LAAP) hydrolyze the N-terminal amino acids and some amino amides the enzymes respectively hydrolyze leucyl- and alanyl-4-nitroanilide substrates. These enzymes occur in microsomes and are also membrane bound they have been used in studies of both hepatotoxicity and nephrotoxicity. They should not be confused with cytosolic leucine aminopeptidase (LAP) this enzyme is an aminopeptidase that hydrolyzes N-amino acid residues of proteins, in particular those with an N-terminal 1-leucine, where l-leucyl-(3-napthylamide is commonly used as substrate. Urinary alanine aminopeptidase is a useful marker of nephrotoxicity (Jung and Scholz 1980). 

Cytosol lactate dehydrogenase leucine aminopeptidase p-glucosidase fructose-1,6 biphosphatase (proximal tubule) pyruvate kinase (distal tubule)... 

Proteasomes are the major cytosolic and nuclear protein degradation machineries and they are also responsible for the proteolysis of misfolded, ER-dislocated (endoplasmic reticulum) proteins [1-3]. Proteasomal protein turnover takes place in an ubiquitin-dependent manner. The proteasome-generated products - ohgopeptides varying in length from 3 to up to 30 amino acid residues - are further processed by aminopeptidases. In higher vertebrates, antigenic peptides are selected from the peptide pool produced by proteasomes and downstream aminopeptidases for presentation on the outer cell surface by major histocompatibility class 1 (MHCl) protein complexes. In this way, proteasomes are essential factors in the detection and eradication of virally infected cells. 

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