Names of Enzymes

1. Names of Enzymes • The name of an enzyme • Usually ends in ­ase. • Describes the function of the enzyme. For example, oxidases catalyze oxidation. • Identifies the reacting substance. For example, • sucrase catalyzes the hydrolysis of sucrose. • Can be a common name, particularly for the • digestive enzymes, such as pepsin and trypsin.

2. alanine transaminase alanine -ketoglutarate pyruvate glutamate Enzyme ClassificationEnzymes are classified by the type of reaction they catalyze. Oxidoreductases Catalyze oxidation-reduction reactions Transferases Catalyze transfer of groups between compounds

3. Hydrolyases Catalyze hydrolysis reactions Enzyme Classification Lyases Catalyze addition or removal of groups without hydrolysis or oxidation

4. triose phosphate isomerase glyceraldehyde-3-phosphate dihydroxyacetone phosphate Isomerases Catalyze rearrangement reactions Enzyme Classification Ligases Catalyze reactions that connect molecules - requires energy input

5. Enzyme Cofactors • Asimple enzyme is an active enzyme that consists only of protein. • Many enzymes are active only when they combine with cofactors such as metal ions or small molecules. • Acoenzymeis a cofactor that is a small organic molecule such as a vitamin. • A holoenzymeis the enzyme + cofactor, an apoenzymeis the enzyme – cofactor.

6. Metal Ions as Cofactors Many active enzymes require a metal ion. Zn2+, a cofactor for carboxypeptidase, stabilizes the carbonyl oxygen during the hydrolysis of a peptide bond.

7. Water-Soluble Vitamins Water-soluble vitamins are • Soluble in aqueous solutions. • Cofactors for many enzymes. • Not stored in the body.

8. Thiamine (Vitamin B1) Coenzyme for decarboxylation reactions Nutritional sources: milk, grains, green vegetables Coenzyme form - thiamine pyrophosphate Deficiency disease: beriberi

9. Riboflavin (Vitamin B2) Coenzyme for oxidation-reduction reactions Nutritional sources: milk, grains, green vegetables Coenzyme form - FAD Deficiency symptoms: dermatitis, tongue inflamation

10. Niacin (Vitamin B3) Coenzyme for oxidation-reduction reactions Nutritional sources: milk, grains, green vegetables Coenzyme forms - NAD+ and NADP+ Deficiency disease: pellegra (rough skin)

11. Pantothenic Acid (Vitamin B5) Coenzyme for transfer of acyl groups Nutritional sources: most foods Coenzyme form - coenzyme A Deficiency symptoms: fatigue, apathy, muscle cramps

12. Pyridoxine (Vitamin B6) Coenzyme for amino group transfer reactions Nutritional sources: milk, grains, green vegetables Coenzyme form - pyridoxal pyrophosphate Deficiency symptom: dermatitis, anemia

13. Biotin (Vitamin B7) Coenzyme for carboxylation reactions Nutritional sources: milk, liver, also produced by intestinal bacteria Coenzyme form - biotin Deficiency symptom: dermatitis

14. Folic Acid (Vitamin B9) Coenzyme for intermolecular one-carbon transfers Nutritional sources: green leafy vegetables, yeast, and produced by intestinal bacteria Coenzyme form - tetrahydrofolate Deficiency symptoms: anemia, diarrhea

15. Vitamin B12 Coenzyme for intramolecular rearrangements Nutritional sources: milk, eggs, other animal products Coenzyme form - 5’deoxyadenosylcobalamin Deficiency disease: pernicious anemia

16. Vitamin C Coenzyme for hydroxylation reactions Nutritional sources: citrus fruits, tomatoes, broccoli Coenzyme form - vitamin C Deficiency disease: scurvy (weakened collagen)

17. pepsinogen pepsin trypsinogen trypsin chymotrypsinogen chymotrypsin procarboxypeptidase carboxypeptidase prothrombin thrombin Insulin proinsulin insulin fibrinogen fibrin ZymogenInactive precursor form of an enzyme or other protein Digestive enzymes Blood-clotting proteins

18. Active Site The active site • Is a region within an enzyme that fits the shape of the reacting molecule called a substrate. • Contains amino acid R groups that bind the substrate. • Releases products when the reaction is complete.

19. E + S ES ES E + P E + S ES E + P Enzyme Catalyzed Reaction: Basic Mechanism The proper fit of a substrate (S) in an active site forms an enzyme-substrate (ES) complex. Within the ES complex, the reaction occurs to convert substrate to product (P). The products, which are no longer attracted to the active site, are released. Overall, substrate is converted to product.

20. E + S ES E + P Enzyme Catalyzed Reaction In an enzyme-catalyzed reaction • A substrate attaches to the active site. • An enzyme-substrate (ES) complex forms. • Reaction occurs and products are released. • An enzyme is used over and over.

21. Enzymes are Biological Catalysts Enzymes are proteins that • Catalyze nearly all the chemical reactions taking place in the cells of the body. • Increase the rate of reaction by providing pathway with a lower the energy of activation.

22. Lock and Key Model In the lock-and-key model of enzyme action, • The active site has a rigid shape. • An enzyme only binds substrates that exactly fit the active site. • Only substrates with the matching shape can fit. • The substrate is the key that fits that lock.

23. Induced-fit Model In the induced-fit model of enzyme action, • Enzyme structure is flexible, not rigid. • Enzyme and substrate adjust the shape of the active site to bind substrate. • Shape changes improve catalysis during reaction. • The range of substrate specificity increases.

24. Enzyme Specificity • A single substrate. (absolute specificity) Example: urease Enzymes may recognize and catalyze • A specific stereoisomer (stereochemical specificity) Example: D-amino acid oxidase • A group of similar substrates.(group specificity) Example: alcohol dehydrogenase • A particular type of bond.(linkage specificity) Example: lipase

25. Substrate Concentration An increase in substrate concentration • Increases the rate of reaction (at constant enzyme concentration). • Eventually saturates an enzyme with substrate to give maximum activity.

26. Enzyme Concentration An increase in enzyme concentration • Increases the rate of reaction (at constant substrate concentration). • Binds more substrate with enzyme.

27. Temperature and Enzyme Action Enzymes • Are most active at an optimum temperature (usually 37°C in humans). • Show little activity at low temperatures. • Lose activity at high temperatures as denaturation occurs.

28. pH and Enzyme Action Enzymes • Are most active at optimum pH. • Contain R groups of amino acids with proper charges at optimum pH. • Lose activity in low or high pH as tertiary structure is disrupted.

29. Optimum pH Values Enzymes in • The body have an optimum pH of about 7.4. • Certain organs, enzymes operate at lower and higher optimum pH values.

30. Feedback Control (Feedback Inhibition) In feedback control • A product acts as a negative regulator. • As the concentration of the end product increases, the end product binds with the first enzyme (E1) in a sequence decreasing the rate of the first reaction.

31. Specific Example of Feedback Inhibition Biosynthesis of Threonine

32. Allosteric Enzymes An allosteric enzyme is • An enzyme in a reaction sequence that binds a regulator substance. • A positive regulator is one that enhances the binding of substrate and accelerates the rate of reaction. • A negative regulator when it prevents the binding of the substrate to the active site and slows down the rate of reaction.

33. Irreversible Inhibition In irreversible inhibition, a substance • Bonds with R groups at the active site. • Destroys enzyme activity.

34. Competitive Inhibition Acompetitive inhibitor • Has a structure that is similar to that of the substrate. • Competes with the substrate for the active site. • Has its effect reversed by increasing substrate concentration.

35. Malonate and Succinate Dehydrogenase Malonate • Is a competitive inhibitor of succinate dehydrogenase. • Has a structure that is similar to succinate. • Inhibition is reversed by adding succinate.

36. Noncompetitive Inhibition Anoncompetitive inhibitor • Binds to a site other than the active site. • Alters the arrangement of groups in the active site. • Doesn’t prevent binding of the substrate, but blocks activity. • Cannot have its effect reversed by adding more substrate.

37. Antibiotics Sulfa drugs - inhibits synthesis of folic acid Some Medical Uses of Inhibitors Cancer chemotherapy Methotrexate (amethopterin) - inhibits synthesis of thymine (part of DNA) 5-Fluorouracil - inhibits DNA synthesis Tetracyclines - inhibit protein synthesis Penicillin - inhibits bacterial cell wall synthesis

38. Neural Transmission using Acetylcholine Release: inhibited by toxin from Clostridium botulinum Binding: inhibited by curare Breakdown: inhibition of acetylcholine esterase Inhibitors: nerve gases (sarin, tabun), insecticides (malathion, parathion)

39. Isoenzymes Isoenzymes • Catalyze the same reaction in different tissues in the body. • Such as lactate dehydrogenase (LDH), which converts lactate to pyruvate, consists of five isoenzymes. • Can be used to identify the organ or tissue involved in damage or disease. • Such as LDH have one form more prevalent in heart muscle and another form in skeletal muscle and liver.

40. Isoenzymes of Lactate Dehydrogenase

41. Diagnostic Enzymes Levels of enzymes CK, LDH, and AST • Are elevated following a heart attack. • Are used to determine the severity of the attack.

42. Diagnostic Enzymes Diagnostic enzymes • Determine the amount of damage in tissues. • That are elevated may indicate damage or disease in a particular organ.