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The biosynthesis of gangliosides was studied in developing biliary cirrhosis in rats 14, 28, and 42 days after bile duct obstruction. The total content and patterns of gangliosides in livers and sera, and the activity of six hepatic ganglioside syn-thases in a cell-free system were determined. Up to 7-fold increased synthase activities were strictly correlated in time and extent with increased total contents of gangliosides in liver and serum. In addition, altered patterns of serum gangliosides were observed. The results clearly demonstrate that the liver is the main source of elevated serum gangliosides in biliary cirrhosis in the rat. Increased hepatic biosynthesis and the secretion of gangliosides into the serum appear to be an important pathogenetic event. Alterations of hepatic enzyme activities indicate that GL 2 and GM 3 synthase regulate total hepatic ganglioside content. However, certain abnormalities in ganglioside patterns which were observed in the liver and sera of cirrhotic animals can not be explained by changes in hepatic enzyme activity. They indicate additional pathobiochemical mechanisms to be involved, e.g., altered hepatocellular processing and/or impaired secretion into bile.

Concentrations, patterns and distribution in different lipoprotein classes of human serum gangliosides were investigated in acute and chronic liver diseases of different etiologies. The total concentrations of gangliosides were moderately elevated in sera of patients with cirrhosis and acute B or NANB virus hepatitis, but almost 3-fold in those with severe cholestasis. Up to three unknown gangliosides appeared in the sera of six out of nine patients with alcoholic cirrhosis. They accounted for 11-27% of total serum gangliosides. In acute viral hepatitis very small amounts of these gangliosides were inconsistently detected. In severe cholestasis (bilirubin greater than 10 mg/dl) the distribution of serum gangliosides was altered in different lipoprotein classes including lipoprotein X (LP(x)). The results indicate that the liver produces serum gangliosides. The diseased liver is supposed to affect the total concentration, pattern and distribution of serum gangliosides in different lipoprotein classes as a result of at least two different pathogenetic events: the qualitative and quantitative alterations of their biosynthesis and secretion into the circulation (cirrhosis); and the alteration of lipoprotein metabolism following cholestasis.