Researchers find a new process to act on the biosynthesis of glycogen

A research team of the University of Barcelona and the University of Oxford have created the method through which they can act directly on the biological process of glycogen formation, thanks to an enzyme activation process through chemical modifications. The study was published in the journal Nature.

Glycogen is the essential macromolecule in energy storage for all bodies. It is the one that accumulates and releases glucose in humans. Deficiencies in glycogen formation can cause metabolic and neurodegenerative diseases.

There is a protein –called glycogenin (GYG)- in the glycogen molecule which conducts a process of self-incorporation of glucose to the molecule (autoglucosylation). While this protein adds glucose it also changes its shape and alters the mechanism of glucose incorporation. Now, through experiments and computational calculations that are carried out at the Barcelona Supercomputer Center (BSC), this mechanism has been unveiled.

Researchers from the University of Oxford Benjamin G. Davis and Wyatt W. Yue could access different states of glycosylation of the GYG protein through an unblocking process of enzyme activation using palladium and using the C-C bond formation in certain amino acids. The UB team, using computational techniques, has modelled these states and has deciphered the mechanism of glycosylation (glucose bonding) through methods of quantum mechanics and molecular dynamics. According to Carme Rovira, ICREA researcher at the Institute of Theoretical and Computational Chemistry of the UB (IQTC-UB), “the experiments show the process of autoglucosylation is surprisingly flexible in the creation and growth of glycogen, which becomes precise while it advances”.

Other participants in the study are the researchers Lluís Raich and Javier Iglesias-Fernández, former doctoral students from the research team led by Rovira, now working at the Free University of Berlin and the University of Girona, respectively.

According to the researchers, “the developed method represents a new way to ‘jump’ into different biology states using chemistry. The study shows how synergy between experiment and computational simulation allows researchers understand biological processes in a precise way”.

Article reference:

M. K. Bilyard, H. J. Bailey, Ll. Raich, M. A. Gafitescu, T. Machida, J. Iglésias-Fernández, S. Seo Lee, C. D. Spicer, C. Rovira, W. W. Yue i B. G. Davis. "Palladium-mediated enzyme activation suggests multiphase initiation of glycogenesis". Nature, October 2018. Doi: 10.1038/s41586-018-0644-7