A nonlinear kinetic model of γ-aminobutyric acid metabolism in a rabbit model of acute liver failure

David G. Covell, Peter Ferenci, Daniel F. Schafer, E. Anthony Jones

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

To investigate the mechanisms by which serum levels of γ-aminobutyric acid (GABA) become elevated in experimental acute liver failure, a multicompartmental model of GABA metabolism has been constructed and used to simulate previously generated data on the kinetics of 3H-GABA uptake by isolated hepatocytes from normal rats and the kinetics of 3H-GABA in the plasma of normal rabbits, rabbits with galactosamine-induced acute liver failure, and rabbits with divascularized livers. Modeling analysis revealed that acute liver failure was associated with values for the mean fractional catabolic rate of GABA, plasma volume, and hepatic extraction of GABA that were 29%, 12%, and 49% less, respectively, than the corresponding control values. The defect in hepatic tissue extraction of GABA was sufficient to account for only 60% of the 10-fold increase in serum GABA levels that occurs in acute liver failure. Furthermore the 10-fold increase in serum GABA levels occured in acute liver failure before the onset of overt hepatic encephalopathy when hepatic extraction of GABA was not appreciably different from that found in normal rabbits. Thus the increase in serum GABA levels that occurs in acute liver failure cannot be attributed to a defect in hepatic extraction of GABA alone. Indeed, the modeling analysis indicated that in acute liver failure there is a 3-8-fold increase in the rate of delivery of GABA to the systemic circulation, but did not indicate its source.

Original languageEnglish (US)
Pages (from-to)121-138
Number of pages18
JournalMathematical Biosciences
Volume75
Issue number1
DOIs
StatePublished - Jul 1985

Fingerprint

Aminobutyrates
liver failure
Enzyme kinetics
Nonlinear Dynamics
Acute Liver Failure
gamma-aminobutyric acid
Rabbit
Kinetic Model
Metabolism
Acute
Liver
gamma-Aminobutyric Acid
Nonlinear Model
serum
metabolism
rabbits
Rabbits
kinetics
Acids
acids

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Cite this

A nonlinear kinetic model of γ-aminobutyric acid metabolism in a rabbit model of acute liver failure. / Covell, David G.; Ferenci, Peter; Schafer, Daniel F.; Anthony Jones, E.

In: Mathematical Biosciences, Vol. 75, No. 1, 07.1985, p. 121-138.

Research output: Contribution to journalArticle

Covell, David G. ; Ferenci, Peter ; Schafer, Daniel F. ; Anthony Jones, E. / A nonlinear kinetic model of γ-aminobutyric acid metabolism in a rabbit model of acute liver failure. In: Mathematical Biosciences. 1985 ; Vol. 75, No. 1. pp. 121-138.
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