A kinetic model of mitochondrial aspartate aminotransferase transmigration in hepatobiliary disorders.
A hypothetical kinetic model of transmigration of mitochondrial aspartate aminotransferase (m-AST) from liver to blood and its elimination from blood was constructed and assessed for prediction by computer simulation. The elimination of m-AST from plasma in healthy rats followed first-order kinetics. Depletion of m-AST from the liver after induction of hepatobiliary disorders in rats with alpha-naphthylisothiocyanate (ANIT) also followed first-order kinetics. In contrast, the changes in metabolic rate in the liver after ANIT administration, as estimated from the plasma indocyanine green clearance, approximated to a second-order time function. Based on these data, the time-dependent change in plasma m-AST activity after ANIT administration was simulated by computer according to a hypothetical kinetic model. The result of computer simulation of the change in plasma m-AST coincided well with that obtained experimentally, suggesting that continuous measurements of m-AST may be helpful to the clinical diagnosis of liver injury.
Numakami
K
K
Department of Clinical Chemistry, Kitasato University School of Allied Health Sciences, Sagamihara City, Japan.
Aoki
Y
Y
Ogawa
Z
Z
Itoh
H
H
D015058:1-Naphthylisothiocyanate; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury; D002779:Cholestasis / Q000139:chemically induced; D003198:Computer Simulation; D007208:Indocyanine Green / Q000378:metabolism; D007527:Isoenzymes / Q000097:blood; D007700:Kinetics; D008107:Liver Diseases / Q000097:blood / Q000201:enzymology*; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D007527:Isoenzymes; D015058:1-Naphthylisothiocyanate; D001219:Aspartate Aminotransferases; D007208:Indocyanine Green