The Enzyme Activity Allosteric Regulation Model Based on the Composite Nature of Catalytic and Regulatory Sites Concept

Abstract

A new kinetic model of enzymatic catalysis is proposed, which postulates that enzyme solutions are equilibrium systems of oligomers differing in the number of subunits and in the mode of their assembly. It is suggested that the catalytic and regulatory sites of allosteric enzymes are of composite nature and appear as a result of subunits joining. Two possible joining modes are postulated at each oligomerization step. Catalytic site may arise on oligomer formed only by one of these modes. Effector acts by fastening together components of certain oligomeric form and increases the life time of this form. It leads to a shift of oligomer equilibrium and increases a proportion of effector-binding oligomers. Effectors-activators bind the oligomers carrying composite catalytic sites and effectors-inhibitors bind the oligomers, which do not carry active catalytic sites. Thus, catalytic activity control in such system is explained by effector-induced changes of a catalytic sites number, but not of a catalytic site activity caused by changes of subunit's tertiary structure. The postulates of the model do not contradict available experimental data and lead to a new type of general rate equation, which allows to describe and understand the specific kinetic behavior of allosteric enzymes as well as Michaelis type enzymes. All known rate equations of allosteric The equation was tested by modeling the kinetics of human erythrocyte phosphofructokinase. It enabled to reproduce quantitatively the 66 kinetic curves experimentally obtained for this enzyme under different reaction conditions.

Dynamic dissociating homo-oligomers and the control of protein function

“…In the same year, Kurganov [69, 70] and Nichol, Jackson and Winzor [71] also proposed mathematical models for the allosteric control of a dissociating/associating oligomer whose different quaternary forms have different functionality. One model proposed by Nichol, Jackson and Winzor [71] and later extended by Drozdov-Tikhomirov [72] accounted for allostery without invoking conformational change in a subunit (Figure 2d). Notably, in 1970 Koshland described dissociation in an allosteric system as means to attenuate the allosteric response [73].…”

“…(c) Frieden’s model that adapts the Monod-Wyman-Changeux model to include dissociation [68]. (d) Allostery without conformational change in the subunits [71, 72]. (e) A model proposed by Koshland that incorporates dissociation in an allosteric model [73].…”

Self-Organization and Fractality in the Metabolic Process of Glycolysis

“…We now study the dependence of the dynamics of the metabolic process of glycolysisgluconeogenesis on the value of parameter 5 l characterizing the activity of gluconeogenesis. The calculations indicate that, as the value of this parameter increases to 0.234, the system passes to the stationary state.…”

“…On the first stage (1), the incoming substance 0 (glucose) is phosphorylated with the help of the enzyme hexokinase to glucose-6-phosphate. The donor of a phosphorylic group is a molecule ATP ( ) (1), (9). This reaction is running irreversibly.…”

“…In the Goldbeter--Lefever model, the origin of autooscillations was explained by the allosteric nature of the enzyme. Some other models are available in [5][6][7].…”