Enzyme leucyl 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. 

Aminopeptidases. There probably is a large number of peptidases with this specificity. Leucyl aminopeptidase has been studied especially well. It attacks leucyl peptides very rapidly, but its specificity is not very strict many different peptides are Split and the enzyme has been used successfully to identify amino terminal residues in proteins. 

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). 

Leucine aminopeptidase preferentially hydrolyses peptide bonds adjacent to an Al-terminal residue that carries a large hydrophilic side chain, in particular a leucyl residue. Commonly used synthetic substrates are leucinamide, leucine 4-nitroanilide and leucine hydrazide. This cytosolic zinc-metalloenzyme has been identified in virtually all animal tissues, and most studies have been performed on the enzyme (Mj 324,000) from bovine lens, which has been crystallized. It consists of 6 identical subunits (M, 54,000 487 amino acids 2 Zrf per subunit), and its catalytically active site is in the C-terminal domain. The enzyme is present in many other cells and tissues, e.g. lung, stomach, kidney intestine, serum and leukocytes. In clinical chemistry, this enzyme is a marker for hepatic cell lysis, and may even be a more sensitive marker for acute hepatitis than the aminotransferases. 

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