Electrophoretic behaviour and partial characterization of disease-associated serum forms of gamma-glutamyltransferase.

We have recently devised an improved procedure for the rapid electrophoretic separation of multiple forms of serum gamma‐glutamyltransferase (GGT). This procedure is based on the separation on cellulose acetate strips, usually employed for lipoprotein electrophoresis, followed by visualization with a fluorescent reagent. The method is highly sensitive and the fractions are more clearly resolved than with other, procedures. Reference intervals have been evaluated in the sera from 142 healthy subjects and the patterns (two GGT forms comigrating with alpha1 and alpha2‐globulin) are reproducible. In 150 sera from patients with various hepatobiliary diseases (including neoplasias), acute pancreatitis and non liver‐involving neoplasias, we observed some disease‐specific GGT forms: an albumin comigrating enzyme (Alb‐GGT) specific of liver neoplasia; a gamma‐globulin comigrating GGT (gamma‐GGT) and a nonmigrating isoform (dep‐GGT) both specifically associated to extrahepatic jaundice. Multiple lipoprotein fraction precipitation showed that beta‐gamma‐ and dep‐GGT are complexes between GGT and low density lipoprotein and very low density lipoproteins (LDL + VLDL), and that some of the alpha1‐GGT from cirrhotic patients is a complex between GGT and high density lipoprotein (HDL). GGT fractions from normal subjects and Alb‐GGT from patients with liver neoplasia do not appear to be complexed with lipoproteins. The amount of GGT complexed with LDL + VLDL differs in various hepatobiliary diseases, and using a cutoff of 20 U/L it is possible to use this test to distinguish non‐cholestatic diseases from liver malignancies (i. e. in monitoring cirrhotics and other high risk groups of patients as to the possible evolution to liver cancer, in patients with gastrointestinal tumor which frequently metastasizes to the liver). Furthermore, treatment of GGT with neuraminidase confirms the association of sialic acid with all the GGT fractions, although Alb‐GGT is more sensitive to this treatment than is beta‐GGT. Our study, indicating the existence of clinical biochemistry correlations between isoenzyme patterns of serum GGT and diseases of hepatobiliary nature including neoplasias, opens up the possibility of enlarging the vocabulary of biochemical signals in these disorders. Furthermore, the lipoprotein‐precipitated fractions of serum GGT are an additional test for discriminating hepatocarcinoma from noncholestatic chronic hepatitis and cirrhosis.