Allosteric enzymes

Against [S] a plot of V₀ for an allosteric enzyme provides a sigmoidal curve rather than the hyperbolic   plots predicted through the Michaelis–Menten equation. The curve has a steep section in the center of the substrate concentration   range  refiecting  the  rapid  increase  in  enzyme  velocity  that occurs  over  a narrow  range  of substrate  concentrations.  This permits allosteric enzymes to be particularly sensitive to little changes in substrate concentration within the physiological range. In allosteric enzymes binding of the substrate molecule to one active site affects the binding of substrate molecules to other active sites in the enzyme; the variant active sites are said to behave cooperatively in acting and binding on substrate molecules cf. binding of O₂ of hemoglobin to the four subunits. Therefore allosteric enzymes are frequent multisubunit proteins with one or more active sites on every subunit. The binding of substrate at one active site induces a conformational modification in the protein which is conveyed to the other active sites altering their affinity for substrate molecules.

Two  models  have  been  put  forward  to  account  for  the  allosteric  effects observed  in proteins.  In the concerted or symmetry model,  first described  through Jeffries Wyman, Jacques Monod and Jean-Pierre Changeaux  who sometimes known to  as  the   Monod-Wyman-Changeaux  (MWC)   model   the   subunits   of  an allosteric  enzyme  can exist in one of only two states that are T and R. T-state subunits are in a tense state which is relatively and compact inactive, therefore R-state subunits  are  in  a expanded, relaxed,  active  state  with  higher  affinity  for  the substrate; no intermediate  states are permitted. In the absence of bound substrate the equilibrium favors the T-state. As substrate binds to every active site in the T- state the equilibrium shifts towards the R-state. All of the subunits modify conformation  in a concerted  manner,  that  implies  in which  the  conformation  of every subunit  is constrained  through its association  with the other subunits;  in other

Figure: Models of allosterism.  (a) The concerted or symmetry model; the squares and circles represent the T- and R-states, respectively. (b) The sequential model; substrate binding progressively induces conformational changes in the subunits.

words,  there  are  no  oligomers   which  concurrently   contain   R-  and  T-state subunits  and  the  molecular  symmetry  of the  protein  is conserved  in during  the conformational  modification.

In the alternative sequential model which is first proposed through Daniel Koshland, sequential modification in structure take place within an oligomeric enzyme as the individual active sites are engaged. The binding of substrate to one site infiuences  the substrate  affinity  of neighboring  active sites without  necessarily inducing a transition  encompassing  the overall enzyme, such that the molecular symmetry   of  the  overall  protein  is  not  necessarily   conserved.  The sequential  model  builds  upon  of enzyme–substrate interaction the induced-fit  hypothesis,  although  the concerted  model  implicitly  assumes  the lock-and-key model  of substrate  binding  to the  enzyme’s  active  site.  In the sequential   model, substrate   binding   induces   a conformational   modification   in a cooperative and subunit interactions arise by the infiuence in which these conformational changes have on neighboring subunits.  Strengths of these interactions depend on the degree of mechanical coupling among subunits. In the  sequential  model  the  enzyme–substrate  binding  affinity  varies  with  the number  of  bound  substrate  molecules,  although  in  the  concerted  model  this affinity  depends  only  on  the  quaternary  state  of  the  enzyme.  The results of learning of a number of allosteric proteins suggest in which most behave according to a combination of the sequential and concerted models.

Allosteric  enzymes  may be controlled  through effector  molecules activators  and inhibitors which bind to the enzyme at a site other than the active site either on the  similar  subunit  or on a various  subunit,  thus  causing  a modification  in the conformation  of the active site that alters the rate of enzyme  activity cf. the binding  of H, CO2 and two, three-bisphosphoglycerate to hemoglobin.An allosteric activator raises the rate of enzyme activity, although an allosteric inhibitor reduces the activity of the enzyme.