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.
Lawrence
G M
GM
School of Life Sciences, Leicester Polytechnic, United Kingdom.
Beesley
A C
AC
Jepson
M A
MA
Walker
D G
DG
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000943:Antigens, Differentiation; D004587:Electrophoresis, Agar Gel; D005260:Female; D005941:Glucokinase / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism*; D006649:Histocompatibility Antigens; D006651:Histocytochemistry; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D017493:Leukocyte Common Antigens; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013194:Staining and Labeling; D013853:Thioacetamide / Q000494:pharmacology*
D000081:Acetamides; D000943:Antigens, Differentiation; D006649:Histocompatibility Antigens; D007527:Isoenzymes; D013853:Thioacetamide; D006593:Hexokinase; D005941:Glucokinase; D017493:Leukocyte Common Antigens