Exploring glycogen biosynthesis through Monte Carlo simulation

Abstract

Glycogen, a complex branched polymer of glucose (average chain length ~10 monomer units), is the blood-sugar reservoir in humans and other animals. Certain aspects of its molecular structure relevant to its biological functions are currently unamenable to experimental exploration. Knowledge of these is needed to develop future models for quantitative data-fitting to obtain mechanistic understanding of the biosynthetic processes that give rise to glycogen structure. Monte Carlo simulations of the biosynthesis of this structure with realistic macromolecular parameters reveal how chain growth and stoppage (the latter assumed to be through both the action of glycogen branching enzyme and other degradative enzymes, and by hindrance) control structural features. The simulated chain-length, pair-distance and radial density distributions agree semi-quantitatively with the limited available data. The simulations indicate that a steady state in molecular structure and size is rapidly obtained, that molecular density reaches a maximum near the center of the particle (not at the periphery, as is the case with dendrimers), and that particle size is controlled by both enzyme activity and hindrance. This knowledge will aid in the understanding of diabetes (loss of blood-sugar control), which has been found to involve subtle differences in glycogen molecular structure.

Controlling the Fine Structure of Glycogen-like Glucan by Rational Enzymatic Synthesis

“…The experimental results of R z and α-amylolysis indicated that the highest molecular density of GnG is found to be near the center of the particle. This result is in accordance with a Monte Carlo simulation of the 3D conformation of a glycogen β-particle, suggesting that the core of glycogen particles has a higher density than the periphery . The formation of a dense center is possible because there are no regulatory enzymes (such as glycogen debranching enzymes) included in the enzyme system of the SP-GP-BE method.…”

Modification of retrogradation property of rice starch by improved extrusion cooking technology

“…glycogen, which is similar to starch in many ways (Zhang et al, 2018)), and so no model can be used for the desired separation. For these reasons, we have simply divided the w(logRh)…”

From Prokaryotes to Eukaryotes: Insights Into the Molecular Structure of Glycogen Particles

“… Besford et al (2015) used small angle X-ray scattering (SAXS) to analyze mouse β-particles, revealing these particles to be randomly branched polymers rather than hierarchical or fractal polymers. In addition, Zhang et al (2018) also used Monte Carlo model to simulate glycogen β particle formation, which also generated randomly branched polymers.…”

“…The technique, involving the scattering of X-rays from all electrons in a sample, allows identification of the pair-distance distribution (i.e., the distribution of all distances between electrons in a single average particle). In addition, Zhang et al (2018) uses the Monte Carlo model to simulate glycogen structure. The result shows that the radial density reaches maximum close to the center of glycogen particles, which is consistent with random growth pattern of glycogen particles ( Zhang et al, 2018 ).…”

“…In addition, Zhang et al (2018) uses the Monte Carlo model to simulate glycogen structure. The result shows that the radial density reaches maximum close to the center of glycogen particles, which is consistent with random growth pattern of glycogen particles ( Zhang et al, 2018 ). Even more recent work by Besford et al (2020) has again shown these same density distributions (pair-distance distributions) for commercial glycogen beta particle preparations that matches the density observed previously.…”