Quantitative modeling and simulation of biochemical processes in the human body

TL;DR

This paper introduces a comprehensive whole-body metabolic model of humans using enzymatic reaction kinetics to simulate fasting effects, aiming to aid drug development and metabolic disorder understanding.

Contribution

It presents a novel systematic and adaptable modeling approach for human metabolism based on enzymatic reactions and organ interactions.

Findings

Simulated effects of fasting on metabolite concentrations.

Analyzed carbohydrate, protein, and lipid storage during fasting.

Demonstrated model's potential for drug development applications.

Abstract

We present a whole-body model of human metabolism that utilizes a system of organs and blood vessels to simulate the enzymatic reactions. The model focuses on key organs, including the brain, heart and lungs, liver, gut, and kidney, as well as muscle and adipose tissue. The model equations are formulated using stoichiometry and Michaelis-Menten kinetics to describe the enzymatic reactions. We demonstrate how the model can be used to simulate the effects of prolonged fasting and intermittent fasting on selected metabolite concentrations and glucose flux. Furthermore, by simulating intermittent fasting the effect on the carbohydrate, the protein and the lipid storage is examined. We propose this method as a simple and intuitive approach for modeling the human metabolism, which is general, systematic and easy to incorporate. This could have potential applications in PK/PD drug development and in understanding metabolic disorders.