Date of Award

2007

Degree Type

Thesis

Department

Chemical and Biomedical Engineering

First Advisor

Belovich, Joanne

Subject Headings

Alcohol -- Metabolism -- Mathematical models, Liver -- Metabolism -- Mathematical models, Phosphofructokinase, Fructose-1,6-Bisphosphatatse, Alcohol metabolism

Abstract

A lumped mathematical model of liver metabolism is presented to analyze the effect of ethanol on metabolic processes of 24 hr fasted rats. The model is developed in two parts. In the first part individual kinetic models for important regulatory steps in the liver metabolic pathways are developed and in second part transport and mass balance equations in the two well mixed domains: tissue and blood, are developed to calculate intermediate metabolite concentrations and fluxes in response to the changes in ethanol and lactate concentrations in the perfusion medium. Part of the model without ethanol metabolism has been validated and published in Chalhoub et al, 2007. The focus of this effort was to illustrate the effect of ethanol metabolism on gluconeogenesis from lactate. The kinetic models developed for phosphofructokinase and fructose 1,6 bisphosphatase have been independently validated with data from the literature, whereas the results of the comprehensive lumped model are compared with the data from Krebs et al (1969). While the lumped model show many important characteristics of ethanol metabolism and predicts the flux of glucose production in the same range, two major contradictions of the simulated results with experimental data are observed. These shortcomings are discussed with appropriate reasoning. The model presented in this thesis is expected to improve the understanding on the effects of ethanol metabolism and provide a practical tool to address alcohol related health issues

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