Enzymes, Regulation, And Inhibition By Nic Oliver And Jamie Gephart

1. Enzymes, Regulation, And Inhibition By Nic Oliver And Jamie Gephart

2. Enzymes A protein that acts as a catalyst for chemical reactions to occur within an organism. Molecular model of lipase

3. Enzyme Roles and Characteristics • Increase the speed of reactions by up to 1020 vs. un-catalyzed reactions • Greatly decrease required energy • Specificity to the type of reaction they catalyze • Ability to be regulated • Lock and key theory

4. Examples of Enzymes and Reactions

5. Nomenclature and Classification • “Earliest discovered enzymes were given names ending with –in” • Ex. Pepsin, trypsin and chymotrypsin • Enzymes are now classified according to the Enzyme Commission system , and placed into a category based on the reaction they catalyze. • Each enzyme name begins with the substrate which is “the substance that undergoes a chemical change catalyzed by the enzyme” • Followed by the functional group that it acts on and the reaction that is catalyzed • Ending with –ase • Ex. Urea amidohydrolase

6. Example IEC name: urea amidohydrolase Substrate: urea Functional group: amide Type of reaction: hydrolysis

7. Enzyme Cofactors • “An enzyme cofactor is a nonprotein molecule or ion required by an enzyme for catalytic activity” • Organic cofactors are called coenzymes • Inorganic cofactors are usually metal ions • The protein portion of enzymes requiring a cofactor is called the apoenzyme • Apoenzyme + Cofactor --> active enzyme

8. Enzyme Cofactors

9. Mechanism of Enzyme Action • Substrate molecules bond to the active site of an enzyme • An active site is where catalysis occurs on the enzyme • Lock and Key Theory • Induced-Fit Theory “Snapshot” of Enzyme Action

10. Mechanism of Enzyme Action • Lock and Key Theory states that “a substrate has a shape fitting that of the enzyme’s active side, as a key fits a lock”. “The lock is the enzyme and the key is the substrate” (Mechanism of Enzyme Action) • Induced-Fit Theory states that “the conformation of an enzyme changes to accommodate an incoming substrate”.

11. Lock and Key Theory vs. Induced-Fit Theory Lock and Key Induced-Fit

12. Enzyme Inhibition “Any substance that can decrease the rate of an enzyme-catalyzed reaction.”

13. Many medications and poisons inhibit enzymes, slowing the reactions to be catalyzed HIV protease in a complex with the protease inhibitor ritonavir. The structure of the protease is shown by the red, blue and yellow ribbons. The inhibitor is shown as the smaller ball-and-stick structure near the centre. Created from PDB 1HXW.

14. Types of Enzyme Inhibition • Irreversible Inhibition • “Substance forms a covalent bond” to a functional group of an enzyme and can not be removed, rendering the enzyme inactive • Examples include deadly poisons such as cyanide and mercury • Medications, including penicillin, act as irreversible inhibitors on bacterial enzymes

15. Examples of penicillin’s various functional groups which inhibit the enzymes that are important in bacteria survival

16. 2. Reversible Inhibitors • Reversibly binds to an enzyme temporarily rendering it inactive, decreasing reaction rates • Either competitive or noncompetitive

17. Competitive inhibitors • Able to bind to active site of enzyme and “compete” with the substrate for the active site (b) Competitive inhibition of succinate dehydrogenase by malonate

18. Reversal of Competitive Inhibition • If concentration of substrate increases then the competitive substance no longer undergoes inhibition at the same rate • Think Le Chatelier’s Principle • As substrate • levels rise, • reaction rates • rise.

19. Noncompetitive Inhibition • It does not resemble the normal enzyme substrate • “Binds reversibly to the surface of an enzyme at a site other than the catalytically active site” • Once bound, the normal enzyme substrate can no longer bind with the enzyme, rendering it inactive • Can not be reversed by the addition of more substrate

20. Noncompetitive Inhibition

21. Negative Feedback Inhibition • “Acts as the thermostat on enzymatic pathways”, either increasing or decreasing product production. • Negative Feedback: When large amount of substrate are present the last enzyme in the pathway will create a product that inhibits the lead enzyme on an allosteric site.

22. Enzyme Regulation • The catalytic activity of enzymes can be regulated • The rate of the reaction and the amount of product formed is controlled by the cell • “Living cells neither synthesize nor break down more material than is required for normal metabolism and growth” (Microbial Genetics)

23. Enzyme Regulation • There are three mechanisms that control how enzyme activity is regulated • Activation of Zymogens • Allosteric Regulation • Genetic Control

24. Activation of Zymogens • Zymogens are the inactive precursor of an enzyme • Zymogens are synthesized and stored until they are needed • If they are stored as active enzymes, they could degrade the internal structures of the cells • When the enzyme is needed, the zymogen is released and activated at the location of the reaction

25. Activation of Zymogens Activation of pancreatic zymogens in the small intestine

26. Allosteric Regulation • An allosteric enzyme is an “enzyme whose activity is changed by the binding of modulators” • Modulators can alter catalytic activity • Modulators that increase activity of an enzyme are called activators • Modulators that decrease activity of an enzyme are called inhibitors • Allosteric regulation allows the concentration of cellular products to be maintained within very narrow limits

27. Allosteric Regulation

28. Genetic Control • Nucleic acids control the amount of proteins produced, including enzymes • By increasing the amount of enzyme molecules present, the production from enzyme-catalyzed reactions will be increased • The name for the process of producing enzymes in response to cellular need is enzyme induction • The rate at which new enzymes are synthesized are regulated by control mechanisms which are turned on or off by the transcription of genes (Regulation)

29. Works Cited Websites “Regulation” Reference http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/E/Enzymes.html “Microbial Genetics” Reference http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit6/genetics/protsyn/regulation/regulation.html “Mechanism of Enzyme Action” Reference http://www.elmhurst.edu/~chm/vchembook/571lockkey.html “Irreversible Enzyme” Reference http://www.elmhurst.edu/~chm/vchembook/573inhibit.html “Negative Feedback” Reference http://www2.estrellamountain.edu/faculty/farabee/biobk/biobookenzym.html Textbook All other non-cited information and quoted definitions “Chemistry for Today: General, Organic, and Biochemistry” 7th Ed. Seager and Slabaugh

30. Works Cited Continued Images “Enzyme Cofactors” http://classes.midlandstech.com/carterp/Courses/bio225/chap05/ss2.htm “Snapshots” http://www.sciencedaily.com/releases/2006/06/060613081650.htm “Enzyme Classification Table” http://www.tutorvista.com/content/biology/biology-iii/cellular-macromolecules/enzymes-classification.php “Zymogens” http://courses.washington.edu/conj/bess/zymogens/zymogens.html “Allosteric Regulation” https://wikispaces.psu.edu/download/attachments/48201949/image-7.jpg “Lock and Key” http://waynesword.palomar.edu/molecu1.htm “Induced Fit” http://www.websters-online-dictionary.org/definitions/Enzyme “Enzyme Inhibition” http://web.fccj.org/~dbyres/enzyme1.html

31. Works Cited Continued Images “HIV Protease” http://upload.wikimedia.org/wikipedia/commons/0/04/HIV_protease_with_bound_ritonavir.png “Penicillin Structure” http://www.flatworldknowledge.com/pub/basics-general-organic-and-bio/421749# “Inhibition of Enzyme Kinetic Energy” https://wikispaces.psu.edu/display/230/Enzyme+Kinetics+and+Catalysis “Competitive Inhibition” http://www.flatworldknowledge.com/pub/basics-general-organic-and-bio/421749# “Reversal of Competitive Inhibition” http://www.websters-online-dictionary.org/definitions/Enzyme “Noncompetitive Inhibition” http://bealbio.wikispaces.com/online+and+upload+enzymes “Negative Feedback” http://charleswardle.com/themes-in-biology-feedback-mechanisms-regulate-biological-systems/