Membrane alanyl aminopeptidases

Membrane alanyl aminopeptidase (microsomal aminopeptidase, amino-peptidase M, EC 3.4.11.2) and peptidyl-dipeptidase A (angiotensin I converting enzyme, EC 3.4.15.1) located in the vascular endothelium and smooth muscle cell surface modulate the levels of vasoactive peptides [23], One of the roles of membrane-bound enzymes is to switch off the action of peptides in the vicinity of the target or to prevent them from gaining access to a region containing receptors that are activated only by locally released peptides. 

Preliminary information useful in prodrug design has been obtained with amino acids attached to model aromatic amines. Thus, N-(naphthalen-2-yl) amides of amino acids (6.1, R=side chain of amino acid, R =H) proved to be of interest as test compounds to monitor peptidase activity such as ami-nopeptidase M (membrane alanyl aminopeptidase, microsomal aminopepti-dase, EC 3.4.11.2) [16][17], In the presence of purified rabbit kidney aminopeptidase M or human cerebrospinal fluid (CSF) aminopeptidase activity, the rate of hydrolysis decreased in the order Ala-> Leu->Arg->Glu-2-naphthyl-amide. Ala-2-naphthylamide, in particular, proved to be a good test compound, as its rate of hydrolysis was influenced by experimental conditions (preparation, inhibitors, etc.), as was the hydrolysis of a number of low-molecular-weight opioid peptides and circulating vasoactive peptides. 

Membrane alanyl Aminopeptidase M, Zinc, cobalt 1,10-Phenanthroline... 

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). 

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