Thioacetamide-induced changes in hepatic hexokinase isoenzymes

In the 48 h following a single i.p. injection of 200 mg of thioacetamide/kg body wt there is a progressive rise in low-Km hexokinase activity and a concomitant decrease in high-Km glucokinase activity. Loss of glucokinase activity occurs as a consequence of its predominantly perivenous zonal distribution in normal liver since it is hepatocytes in this region of the acinus that are selectively damaged by thioacetamide. Increased low-Km activity is mainly present in inflammatory infiltrates which invade perivenous and mid-zone regions in response to tissue injury. Low- and high-Km hexokinase activities return to control levels 10 days after thioacetamide treatment when the infiltration zones disappear and necrotic perivenous hepatocytes are replaced by cells with normal morphology. Changes in low- and high-Km hexokinase activities induced by thioacetamide thus appear to primarily reflect alterations in cell population rather than changes in gene expression within existing hepatocytes.