Alanine aminopeptidase

McClellan, J.B.J., and C.W. Garner. 1980. Purification and properties of human intestine alanine aminopeptidase. Biochim Biophys Acta 613 160. 

Occupational exposure to chromium(III) or chromium(O) does not appear to be associated with renal effects. No renal impairment based on urinary albumin, retinol binding protein, and renal tubular antigens was found in 236 workers employed in the ferrochromium production industry where ferrochromite is reduced with coke, bauxite, and quartzite. The mean airborne concentration of chromium in various sample locations was 0.075 mg chromium(III)/m3 chromium(VI) was below the detection limit of 0.001 mg chromium(VI)/m3 at all locations (Foa et al. 1988). Workers employed in an alloy steel plant with a mean exposure of 7 years to metallic chromium at 0.61 mg chromium(0)/m3 and to other metals had normal urinary levels of total protein and p2-microglobulin, enzyme activities of alanine-aminopeptidase, N-acetyl-P-D-glucosaminidase, gammaglutamyl-transpeptidase, and P-galactosi-dase (Triebig et al. 1987). In boilermakers exposed to chromium(O), no increase in urinary levels of... 

Serum creatinine and BUN, the most common indicators of renal function used in both clinical and preclinical safety laboratory panels, are relatively insensitive markers of injury, particularly for the renal tubules. Urinary measurements of alanine aminopeptidase and A-acetyl-beta-D-glucosaminidase and kidney injury molecule-1 (KIM-1) can provide much more sensitivity when nephrotoxicity is a potential safety concern [28,29], These are also suitable for safety monitoring in early-phase human trials if preclinical studies validate such use to monitor product nephrotoxicity. 

Mueller PW, Macneil ML, Steinberg KK (1986) Stabilization of alanine aminopeptidase, gamma glutamyltranspepti-dase, and N-acetyl-fi-D-glucosaminidase activity in normal urines. Archiv Environ Contam Toxicol 15 343-347 Mueller PW, MacNeil ML, Steinberg KK (1989) N-acetyl-beta-D-glucosaminidase assay in urine urea inhibition. J Anal Toxicol 13 188-190... 

Enzymuria has been reported after the intravascular administration of high-osmolar or low-osmolar contrast media (180). The study suggested that the brush-border enzyme gamma-glutamyl transpeptidase is a better marker for tubular toxicity due to contrast media than alanine aminopeptidase. However, no relation has been established between a reduction in glomerular filtration rate, a rise in serum creatinine (the characteristic features of contrast nephrotoxicity), and the presence of enzymuria. It has been argued that the detection of urinary enzymes is of httle importance to the clinical assessment and management of contrast medium nephrotoxicity (161). 

When considering the application of urinary enzymes to monitor subtle renal dysfunction and/ or to clarify mechanisms of nephrotoxicity, only a limited number of enzymes have been generally accepted as valuable urinary biomarkers. These include lactic dehydrogenase, N-acetyl-P-l>glucosarriitiidase (NAG), alanine aminopeptidase (AAP), intestinal alkaline phosphatase, glutathione-S-transferase, gamma-glutamyl transferase and fructose-l,6,-biphosphatase. 

Urine Urinalysis with microscopic examinination of urine sediment Albumin Retinol binding protein N-acetyl-p-D-glucosaminidase Alanine aminopeptidase Osmolality Creatinine Glomerulus Proximal tubule Proximal tubule Proximal tubule Distal tubule Control for urine concentration... 

Davey PG, Cowley DM, Geddes AM,Terry J. Clinical evaluation of P2-microglobulin, murmamidase,and alanine aminopeptidase as markers of gentamicin nephroxicity. Contrib Nephrol 1984 42 100-106. 

There are numerous methods to determine the nephrotoxic potential of a chemical or to study the mechanism(s) by which a chemical induces nephrotoxicity. In humans, the concern is most often related to either drug-induced or occupationally associated nephrotoxicity. Evaluation of nephrotoxicity in humans is limited primarily to the measurement of urinary changes (e.g., volume, enzymes, protein, etc.), BUN or serum creatinine concentrations, creatinine clearance, or renal biopsy. The measurement of an increase in urinary N-acetyl-jS-D-glucosaminidase (NAG) or alanine aminopeptidase (AAP) levels,... 

Tubular function p-Ami noh ippu rate N- -Methyinicotinamide (NMN) Tetraethylammonium (TEA) /J2-Microglobulin Retinol-binding protein (RBP) Protein HC (ai-microglobulin) N-Acetylglucosaminidase (NAG) Alanine aminopeptidase (AAP) Adenosine binding protein (ABP)... 

Numerous urinary enzymes such as A-acetylglucosaminidase (NAG), alanine aminopeptidase (AAP), alkaline phosphatase (AP),... 

AAP alanine aminopeptidase ABW actual body weight ACE angiotensin-converting enzyme Alb serum albumin concentration AP alkaline phosphatase... 

The determination of alanine aminopeptidase (AAP, EC 3.4.11.14) is of importance in the rapid diagnosis of liver and bile diseases. Common assays involve the coupling of alanine hydrazide cleavage with a chro-mogenic reaction. Kirstein (1987) proposed indicating the rate of hydrazine formation electrochemically. In contrast to an amperometric urea sensor based on this indication method (see Section 3.1.21), the pH value in the near-electrode space remains unchanged while the concentration of electrode-active hydrazine rises. The incubation period for AAP assay is lowered to half of that needed in the conventional method, the two correlating with r = 0.994. 

DHP=Dehydrogenase activity in pore-water DHgS= Dehydrogenase activity in sediment AP=Alanin- Aminopeptidase activity in pore-water AV=Alanin- Aminopeptidase, D1 value of dilution series AS=Alanin- Aminopeptidase activity in sediment PGP=p-Glucosidase activity in pore-water PGV=p-Glucosidase activity, D1 value of dilution series PGS=p-Glucosidase activity in sediment PR=Protease activity... 

Precision Standardization (accuracy) Interference Technical performance (automation) Cost Alanine aminopeptidase (AAP) Alkaline phosphatase y-glutamyltransferase (GGT) Maltese Trehalase brush border... 

Jung K, Scholz D. An optimized assay of alanine aminopeptidase activity in the urine. Clin Chem 1980 26 1251-1254. 

Mueller PW. MasNeil ML, Steinberg KK. Stabilization of alanine aminopeptidase. y-glutamyltransferase and N-acetyl-ji-D-glucosaminidase in normal urine. Arch Environ Contam Toxicol 1986 15 343-347. 

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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