Hepatic activity and mRNA expression of aspartate aminotransferase isoenzymes in alcoholic and nonalcoholic liver disease.
In liver and serum, AST activity is dependent on two isoenzymes, which are mitochondrial and cytosolic in nature. In an attempt to explain the well-known increase of serum mitochondrial AST-to-total AST ratio in chronic alcoholism (which is due to a specific increase of the mitochondrial isoenzyme), we analyzed: (a) liver and serum AST, ALT and glutamate dehydrogenase activities in 23 active drinkers with minimal liver changes, 11 alcoholic patients with cirrhosis who had stopped drinking, 18 nonalcoholic patients with viral chronic hepatitis and 11 subjects with normal livers; and (b) the expression of messenger RNAs for AST isoenzymes in the corresponding liver samples. Enzymatic activities were decreased in the liver irrespective of the origin of the liver disease. In patients with viral chronic hepatitis (or in those with alcoholic cirrhosis when abstinent), variations in liver proteins and messenger RNAs paralleled significant decreases in mitochondrial AST, ALT and glutamate dehydrogenase and a nonsignificant decrease of cytosolic AST. In alcoholic patients with minimal liver changes, the significant decrease of hepatic cytosolic AST, ALT and glutamate dehydrogenase activities contrasted with a close-to-normal liver mitochondrial AST activity; the increased amounts of mitochondrial AST messenger RNA give evidence for a pretranslational mechanism of regulation, indicating a possible increase in the total production of mitochondrial AST in the liver. The decrease of hepatic cytosolic AST activity was statistically significant only in alcoholic patients without cirrhosis who had a normal cytosolic AST mRNA level, thus suggesting a contributory role of translational or posttranslational regulation. In conclusion, regulation of AST isozymes during liver disease is complex, including differential, pretranslational and translational or posttranslational mechanisms.
Pol
S
S
Unité d'Hépatologie, Hôpital Laënnec, Paris, France.
Nalpas
B
B
Vassault
A
A
Bousquet-Lemercier
B
B
Franco
D
D
Lacour
B
B
Berthelot
P
P
Hanoune
J
J
Barouki
R
R
D001219:Aspartate Aminotransferases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008107:Liver Diseases / Q000097:blood / Q000201:enzymology*; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism*; D012016:Reference Values
D007527:Isoenzymes; D012333:RNA, Messenger; D001219:Aspartate Aminotransferases