Serum leucine aminopeptidases

SK Gupta, M Aziz, AA Khan (1989) Serum leucine aminopeptidase estimation a sensitive prognostic indicator of invasiveness in breast carcinoma, Indian J Pathol Microbiol 32 301—305... 

ENl 16 Mauck, J., Warren, H. and LaTart, D. (1992). Development of a thin-film colorimetric assay for serum leucine aminopeptidase. Clin. Chem. 38, 985-986, Abstr. 217. 

K23. Kowlessar, O. D., Haeffner, L. J., and Riley, E. M., Localization of serum leucine aminopeptidase, 5-nucleotidase and nonspecific alkaline phosphatase by starch-gel electrophoresis. Clinical and biochemical significance in disease states. Ann. N.Y. Acad. Sci. 94, 836-843 (1961). 

Enzymes activities are particularly sensitive to the anticoagulant used in collecting the specimen. Heparin inhibits acid phosphatase (W16) and muramidase (Z5). Amylase activity is inhibited by oxalate or citrate (MIO), and lactic dehydrogenase and acid phosphatase lose activity in oxalate (C2). Alkaline phosphatase is stable in oxalate, oxalate-fluoride, or heparin, but 25 mAf citrate inhibits 50% of the activity, and as little as 50 mlf EDTA is completely inhibitory (B19). Leucine aminopeptidase is inhibited by EDTA, as is creatine phosphokinase (F3). Amylase activity has been reported to be only 83% of that in serum when oxalate or citrate-plasma is used (MIO). Heparin plasma appears to have no inhibitory effect. Despite the fact that clotting factor V is not stable in oxalate or EDTA, these are often used as anticoagulants to obtain plasma for prothrombin determinations (Z2, Z4). 

Measurement of serum y-GT activity has clinical significance. The enzyme is present in all tissues, but the highest level is in the kidney however, the serum enzyme originates primarily from the hepatobiliary system. Elevated levels of serum y-GT are found in the following disorders intra- and posthepatic biliary obstruction (elevated serum y-GT indicates cholestasis, as do leucine aminopeptidase, 5 -nucleotidase, and alkaline phosphatase) primary or disseminated neoplasms some pancreatic cancers, especially when associated with hepatobiliary obstruction alcohol-induced liver disease (serum y-GT may be exquisitely sensitive to alcohol-induced liver injury) and some prostatic carcinomas (serum from normal males has 50% higher activity than that of females). Increased activity is also found in patients receiving phenobarbital or phenytoin, possibly due to induction of y-GT in liver cells by these drugs. 

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. 

---