Siest G. Associations between serum gammaglutamyltransferase and apolipoproteins: relationships with hepatobiliary disease. Clin Chem

We studied the association between -glutamyItransferase (GGT) and apolipoproteins A or B in serum of 42 patients with various hepatobiliary diseases. Binding of the enzyme to apolipoprotein A is not related to a clearly defined disease, but appears to be mainly influenced by the ratio of total cholesterol to GGT activity. An important fraction of GGT activity is associated with apolipoprotein B in patients with icteric or anicteric cholestasis. Conversely, in noncholestatic patients, the percentage of apolipoprotein B-bound GGT activity is low. Addition of the “heavy ” form of GGT, obtained by solubilizing the membrane-bound enzyme with deter-gents, to a serum with low GGT activity led to the binding of the enzyme only to apolipoprotein A. The “light ” form of GGT, obtained by limited proteolysis of the “heavy ” form and added to the same serum, did not bind to either apolipopro-tein A or apolipoprotein B. Thus, the association between the serum enzyme and apolipoprotein A apparently results from nonspecific aggregation of the amphiphilic “heavy ” form of the enzyme. The origin of the apolipoprotein B-GGT com-plexes found in cholestatic patients needs further investiga-tion. Addftlonal Keyphrases: cholesterol. cholestasis sfeatosis cirrhosis biliru bin isoenzymes Many studies on the multiple molecular forms of serum y-glutamyltransferase (GOT, EC 2.3.2.2) have been reported, but with conflicting results with regard to their number and their clinical significance (reviewed in 1). GGT in serum is generally thought to originate from the liver, because activities are increased only in hepatobiliary diseases (2,3), but the origin of its heterogeneity is still a matter of debate. This heterogeneity apparently results from three types of phenomena occurnng simultaneously: aggregation of the enzyme with other serum components (e.g., lipoproteins), variation in the degree of sialylation of the molecule (4), and proteolytic modification of the enzyme in vivo or during storage of the samples (5, 6). There are several reports of binding of GGT to lipids or lipoproteins (7-15). Thus the enzyme was found to be associated with high-density lipoproteins or apolipoprotei