Enzymes Released from Diseased Liver Tissue

Enzymes Released from Diseased Liver Tissue... 

Determination of LDH Lactate dehydrogenase (LDH) catalyzes the equilibrium reaction of pyruvate to lactate. The activity of serum LDH is due to the presence of the enzyme released from damaged organs and tissues such as liver, heart, skeletal muscle, erythrocytes, etc. because LDH is located in the cytoplasm of the cells. Therefore, the activity of LDH is useful for screening for the existence of cell injuries, estimation of damaged tissues, and evaluation of treatment of diseases. LDH has five isoenzymes, and their patterns are of diagnostic importance. 

The relation between tissue injury and the appearance of enzymes in the circulation is most clearly seen in the condition of myocardial infarction, in which a relatively short episode of damage is followed by a rapid transfer of enzymes to the circulatory system. About 24 hours after a myocardial infarction, the pattern of relative activity of various enzymes in the circulatory system closely resembles that in the myocardial tissue. These relationships are less clearly recognized in other conditions, such as chronic liver disease, in which enzyme release is a process that continues for a period of time. The pattern of relative enzyme activities in serum in chronic disease may also become distorted by differential rates of removal of enzymes from the circulation and possibly also by differential changes of rates of enzyme synthesis in the affected tissue. 

Alkaline phosphatases (ALP) are a group of enzymes found primarily in the liver (isoenzyme ALP-1) and bone (isoenzyme ALP-2). There are also small amounts produced by cells lining the intestines (isoenzyme ALP-3), the placenta, and the kidney (in the proximal convoluted tubules). What is measured in the blood is the total amount of alkaline phosphatase released from these tissues into the blood. As the name implies, this enzyme works best at an alkaline pH (pH 10), and thus the enzyme itself is inactive in the blood. Alkaline phosphatase acts by splitting off phosphorus (an acidic mineral), creating an alkaline pH. The primary importance of measuring alkaline phosphatase is to check the possibility of bone or liver diseases. ... 

Because the pattern and degree of elevation of enzyme activity vary with the type of liver disease, their measurement is extremely helpful in the recognition and differential diagnosis of liver damage. A number of factors govern the ability of Uver enzymes to assist in diagnosis including their (1) tissue specificity, (2) subcellular distribution, (3) relative activity of enzyme activity in liver and plasma, (4) patterns of release, and (5) clearance from plasma. 

The mechanism of release of membrane-bound enzymes such as GGT and ALP into the circulation is less well understood. There appears to be increased synthesis of GGT and ALP in diseased human liver. How this enhanced synthesis of tissue-bound enzymes translates into increased activity in plasma is not clear. However, fragments of hepatocyte niembrane rich in GGT and ALP activity have been detected in plasma of patients with cholestasis, a process that may be a result of membrane fragmentation by bile acids. Furthermore, bile acids, which are detergents, could solubilize and release GGT and ALP from plasma membranes. In vitro studies of membranes treated with bile acids demonstrate that this possibility exists. ... 

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