Effects of a high protein diet and liver disease in an in silico model of human ammonia metabolism

Theoretical Biology & Medical Modelling
Jeddidiah W D Griffin, Patrick C Bradshaw

Abstract

After proteolysis, the majority of released amino acids from dietary protein are transported to the liver for gluconeogenesis or to peripheral tissues where they are used for protein synthesis and eventually catabolized, producing ammonia as a byproduct. High ammonia levels in the brain are a major contributor to the decreased neural function that occurs in several pathological conditions such as hepatic encephalopathy when liver urea cycle function is compromised. Therefore, it is important to gain a deeper understanding of human ammonia metabolism. The objective of this study was to predict changes in blood ammonia levels resulting from alterations in dietary protein intake, from liver disease, or from partial loss of urea cycle function. A simple mathematical model was created using MATLAB SimBiology and data from published studies. Simulations were performed and results analyzed to determine steady state changes in ammonia levels resulting from varying dietary protein intake and varying liver enzyme activity levels to simulate liver disease. As a toxicity reference, viability was measured in SH-SY5Y neuroblastoma cells following differentiation and ammonium chloride treatment. Results from control simulations yielded steady...Continue Reading

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Citations

Nov 26, 2020·Journal of Experimental Pharmacology·Omid FarshadAkram Jamshidzadeh

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Methods Mentioned

BETA
deamination
Protein Assay

Software Mentioned

MATLAB
GraphPad Prism
Excel
SimBiology

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