Serum gamma-glutamyl-transpeptidase (gamma-GTP) from patients with various hepatobiliary diseases was fractionated by molecular size using HPLC to investigate the heterogeneity of serum gamma-GTP. Serum gamma-GTP eluted with HPLC showed essentially 3 elution peaks of different molecular size. In the sera of normal patients, there was little gamma-GTP in the high molecular fraction, and most occurred in the low molecular fraction. Intermediate molecular gamma-GTP appeared only in the sera of patients with hepatobiliary disease. In the sera of patients with extrahepatic biliary obstruction, the percentage of high molecular gamma-GTP to total serum gamma-GTP activity was higher than that of other patients. High molecular gamma-GTP increased in the sera of patients with extrahepatic biliary obstruction. Intermediate molecular gamma-GTP appeared in the relatively higher molecular fraction in the sera of patients in whom alcohol consumption might have caused serum gamma-GTP increase, and in the relatively lower molecular fraction in the sera of patients with extrahepatic biliary obstruction. It was concluded, therefore, that the position of elution of intermediate molecular gamma-GTP corresponded to the morbid state. It was shown that intermediate molecular gamma-GTP appeared in the relatively low molecular fraction, corresponding to the increase of serum total bile acids concentration.

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