Effect of molecular crowding on the enzymes of glycogenolysis

• Published in: Biochemistry (Moscow) Vol. 72; no. 13; pp. 1478 - 1490
• Main Author: Chebotareva, N A
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.12.2007
• Subjects: Animals; Betaine - chemistry; Cytoplasm - metabolism; Enzymes - chemistry; Glycogenolysis; Humans; Kinetics; Ligands; Methylamines - chemistry; Molecular Conformation; Osmosis; Phosphorylase b - chemistry; Phosphorylase Kinase - chemistry; Protein denaturation; Protein Interaction Mapping; Proteins; Thermodynamics
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/s0006297907130056

Cell cytoplasm contains high concentrations of macromolecules occupying a significant part of the cell volume (crowding conditions). According to modern concepts, crowding has a pronounced effect on the rate and equilibrium of biochemical reactions and stimulates the formation of more compact structures. This review considers different aspects of the crowding effect in vivo and in vitro, its role in regulation of cell volume, the effect of crowding on various interactions, such as protein-ligand and protein-protein interactions, as well as on protein denaturation, conformation transitions of macromolecules, and supramolecular structure formation. The influence of crowding arising from the presence of high concentrations of osmolytes on the interactions of the enzymes of glycogenolysis has been demonstrated. It has been established that, in accordance with predictions of crowding theory, trimethylamine N-oxide (TMAO) and betaine highly stimulate the association of phosphorylase kinase (PhK) and its interaction with glycogen. However, high concentrations of proline, betaine, and TMAO completely suppress the formation of PhK complex with phosphorylase b (Phb). The protective effect of osmolyte-induced molecular crowding on Phb denaturation by guanidine hydrochloride is shown. The influence of crowding on the interaction of Phb with allosteric inhibitor FAD has been revealed. The results show that, under crowding conditions, the equilibrium of the isomerization of Phb shifts towards a more compact dimeric state with decreased affinity for FAD.