Stochastic modelling of a three-dimensional glycogen granule synthesis and impact of the branching enzyme

• DOI: 10.1101/2022.10.31.514469
• Publication Date: 2022-11-01T19:55:15Z
• Authors: Yvan Rousset; Oliver Ebenhöh; Adélaïde Raguin
• Keywords: Glycogen branching enzyme; Branching (polymer chemistry); Granule (geology); Branching process; Glycogen debranching enzyme

Abstract In humans, glycogen storage diseases result from metabolic inborn errors, and can lead to severe phenotypes lethal conditions. Besides these rare diseases, is also associated widely spread societal burdens such as diabetes. Glycogen a branched glucose polymer synthesised degraded by complex set of enzymes. Over the past 50 years, structure has been intensively investigated. Yet, interplay between related enzymes still be characterised. this article, we develop stochastic coarse-grained spatially resolved model biosynthesis following Gillespie algorithm. Our study largely focusses on role branching enzyme, first investigates properties with generic parameters, before comparing it in vivo experimental data mice. It arises that ratio synthase over enzyme activities drastically impacts granule. We deeply investigate mechanism parametrise using distinct lengths. Not only do consider various possible sets values for lengths, but rules apply them. show how combining them finely tunes macromolecular structure. Comparing confirms accurately reproduce chain length distributions wild type Additional granule obtained fit are good agreement typically reported literature. Nonetheless, find must more flexible than usually reported. Overall, demonstrate distribution an imprint activity mechanism. methods applied any set, could particular contribute characterise mechanisms responsible disorders. Author summary granule-like macromolecule made 10,000 50,000 units arranged linear chains. serves energy many species, including humans. Depending physiological conditions (hormone concentrations, level, etc.) granules either or degraded. Certain disorders abnormal structures, structural might impact dynamics release storage. To capture properties, propose computational relying random nature biochemical reactions. The represented three dimensions at scale. Granules produced under action enzymes, mostly focus those formation new branches. Specifically, their molecular With model, able observed certain in-vivo biophysical approach complements studies may processes