An investigation of the effects of irradiation on serum leucine aminopeptidase (LAP).

Abstract

The presence of a circulating proteolytic enzyme acting upon the end-products of protein metabolism has been known for many years. In 1929 an enzymatic dipeptide acting directly on L-leucylglycine was identified and named leucine aminopeptidase. This enzyme has not yet been isolated in its pure state, but can be assayed in serum and urine by a colorimetric determination (2). Leucine aminopeptidase (LAP) is found in all human tissue, with highest concentrations in the liver, biliary tract, and duodenal mucosa. Although there have been considerable investigation and documentation of the biochemical and physical properties of the enzyme, its specific function in the blood remains unknown (1). Since leucine aminopeptidase is excreted by the liver into the bile, obstructions in the biliary tract result in elevated serum levels of the enzyme. Attempts have been made to determine whether increases in the blood can be interpreted as evidence of biliary or pancreatic disease when clinical manifestations such as jaundice are absent. Rutenburg et al. (1958) claimed that the degree and duration of serum LAP elevations in jaundiced patients helped distinguish between carcinoma of the pancreas and other icteric conditions (6). Other authors contend that the LAP test merely denotes obstructive disease in the biliary tract, without reference to the cause of obstruction (4, 7). Persistently high LAP readings have been noted in the following conditions: carcinoma involving the head and, to a lesser extent, the tail of the pancreas; carcinoma of the gallbladder and biliary tree ; choledocholithiasis; inflammatory disease of the biliary tract; primary liver disease, such as infectious mononucleosis and infectious hepatitis; remote cancer metastatic to the liver (3, 4, 5). Serum LAP is not ordinarily elevated in patients with malignant disease unrelated to the hepato-biliary-pancreatic system, although high readings are occasionally obtained. Transient LAP elevations are noted in the third trimester of pregnancy and in the immediate postoperative state (8). Of special interest is the evidence that a markedly elevated LAP in an anicteric patient with cancer suggests metastatic deposits in the liver (4). Corroboration of this contention would provide the clinician with a simple test to help evaluate a course of treatment for the patient with malignant disease. Since LAP is a proteolytic enzyme, a nonspecific elevation may occur as a reflection of tissue destruction in areas remote from the hepato-biliary system. Injury to hepatic cells has been shown to result in extravasation of the enzyme into the circulation, with a subsequent rise in the serum concentration (5). The elevation in serum LAP following surgery may be equated to the degree of tissue trauma during the procedure. Controlled, localized tissue injury is inherent in radiation therapy of malignant disease.