Allosteric enzymes

Here is the brief description about Allosteric Enzymes.
depicted with some useful graphs.

1. ALLOSTERIC ENZYMES Presented By: Inchara R 6 th Semester Molecular Biology 23/05/2020 Guided By: Prof. Cletus D’Souza Dept. of Molecular Biology

2. CONTENTS Introduction Allosteric effector Properties of allosteric enzyme Kinetic property of allosteric enzyme Classes of allosteric enzymes Allosteric regulation mechanism Feedback regulation Aspartate transcarbamoylase Conclusion References Acknowledgement

3. INTRODUCTION Fig 01 : Generic allosteric enzyme

4. ALLOSTERIC EFFECTOR Allosteric Enzymes functions through reversible, non-covalent binding of regulatory compounds called Allosteric effector or Allosteric modulator. There are 2 types of allosteric effectors: Positive (+) allosteric effector : The enzyme activity is increased when a positive allosteric effector binds at the allosteric site known as activator site. Negative (-) allosteric effector : The enzyme activity is decreased when a negative allosteric effector binds at the allosteric site called inhibitor site and inhibits the enzyme activity.

5. PROPERTIES The properties of allosteric enzymes are significantly different from those of simple non regulatory enzymes. Catalyze essentially irreversible reactions. Generally contain more than one polypeptide chain. There can be more than one allosteric sites present in an enzyme molecule. Allosteric enzymes are generally larger & more complex than non-allosteric enzymes. Most have 2 or more subunits. An allosteric site is specific for its ligand, just as the active site is specific for its substrate.

6. KINETIC PROPERTY Graph 01 : Kinetic profie of an allosteric enzyme Allosteric enzymes display a sigmoidal dependence of reaction velocity on substrate concentration . Eq 01 : Michaelis – Menten equation o

7. CLASSES OF ALLOSTERIC ENZYMES They are divided into two classes based on the influence of allosteric effector on Km and Vmax . K-class of allosteric enzymes: T he effector changes the Km and not the Vmax . Double reciprocal plots, similar to competitive inhibition are obtained. Example: P hosphofructokinase. V-class of allosteric enzymes : The effector alters the Vmax and not the Km. Double reciprocal plots resemble that of non-competitive inhibition. Example: Acetyl CoA carboxylase .

8. Graph 02 : V-class of allosteric enzymes Graph 03 : K-class of allosteric enzymes The effects of positive and negative effectors on allosteric enzyme: Graph 02 - Vmax is altered Graph 03 - The substrate concentration that gives half maximal velocity (K0.5) is altered. o o

9. ALLOSTERIC REGULATION MECHANISM Fig 02 : Two Types of Allosteric regulation- Inhibition and Activation .

10. There are two types of allosteric regulation on the basis of substrate and effector molecules : Homotropic Regulation: In a homotropic interaction, the same ligand positively influences the cooperativity between different modulator sites on the enzyme. Fig 03 : Homotropic allosteric effector

11. Heterotropic Regulation : Heterotropic interaction refers to the effect of one ligand on the binding of a different ligand . Fig 04 : Heterotropic allosteric effector

12. There are two models proposed for the mechanism of regulation of allosteric enzymes . 1. Simple Sequential Model : Proposed by Koshland , Némethy and Filmer in 1966. The T →R shift occurs to each subunit as it binds the ligand Fig 05 : The sequential binding of the ligand in a simple sequential model T State R State

13. Concerted or Symmetry Model : This model was proposed by Jacques Monod , Jeffries Wyman , and Jean-Pierre Changeux . Fig 06 : MWC Model of allosteric enzyme in R form (active form)

14. FEEDBACK REGULATION Fig 07 : Feedback inhibition (a) Sequential inhibition (b) in branched pathway

15. ASPARTATE TRANSCARBAMOYLASE Structure: Fi g 08 : ATCase (C 6 R 6 ) (A) Top View (B) Side View

16. Kinetics : The T-to-R State Transition in ATCase Fig 09 : The R State and the T State Are in Equilibrium. Even in the absence of any substrate or regulators, aspartate transcarbamoylase exists in an equilibrium between the R and the T states .

17. N-( Phosphonacetyl )-L-aspartate (PALA): Fig 10 : Structure of ATCase -PALA Complex. PALA binding stabilizes the R state.

18. Fig 11 : Formation of N- carbamoyl aspartate by Aspartate transcarbomylase ( ATCase ), the committed step in the pyrimidine biosynthesis & a key control point. Mechanism:

19. Graph 04 : Effect of CTP & ATP on ATCase kinetics. ATCase Displays Sigmoidal Kinetics : A plot of Initial velocity Vo against substrate concentration of the allosteric enzyme Aspartate transcarbomylase .

20. CONCLUSION

21. REFERENCES Bhagavan N . V. & Chung- Eun Ha. 2001. Essentials of Medical Biochemistry with Clinical Cases, 2nd Edition, Elsevier publication, London, UK, 719pp. Jeremy M. Berg , John L. Tymoczko & Lubert Stryer . 2007. Biochemistry, 6th edition, W. H. Freeman & Company, New York, USA, 1158pp. Satyanarayana U. & Chakrapani U . 2007 . Biochemistry, Books and allied (P) Ltd, Kolkata, India, 794pp. Hames B.D . & Hooper N.M . 2000 . Biochemistry, 2nd Edition, BIOS Scientific Publishers Limited, New York, USA, 433pp.

22. https:// alevelchemistry.co.uk/definition/allosteric-enzymes/ https :// byjus.com/neet/allosteric-enzyme/ https://en.wikibooks.org/wiki/Structural_Biochemistry/Enzyme_Regulation/Allosteric Control https :// www.slideshare.net/Haddies/allosteric-enzymes https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/allosteric-enzyme

23. ACKNOWLEDGEMENT I would like to thank the dept. of Molecular Biology for providing this opportunity to present this seminar. I would also like to thank my guide Prof. Cletus D’Souza for his valuable guidance. Thank you one and all . 