Chapter 13: Enzymes!!

1. Chapter 13: Enzymes!!

2. What are enzymes? • Usually proteins (exception = ribozymes) • Biological Catalysts • Facilitate reactions under physiological conditions that would require very harsh conditions in the laboratory

3. Enzymes biological catalysts responsible for supporting almost all of the chemical reactions that maintain organismall homeostasis. The macromolecular components of almost all enzymes are composed of protein, except for a class of RNA modifying catalysts known as ribozymes. Ribozymes are molecules of ribonucleic acid that catalyze reactions on the phosphodiester bond of other RNAs. Almost every significant life process is dependent on enzyme activity.

4. Stryer Fig. 8.3

6. Functions of Catalysts • Lower the Ea for a reaction • Are regenerated • Do not affect equilibrium position

7. Table 13-3 Enzyme Classification According to Reaction Type. Page 470

8. Figure 13-1 An enzyme–substrate complex illustrating both the geometric and the physical complementarity between enzymes and substrates. Page 460

9. Number Classification Biochemical Properties 1. Oxidoreductases Act on many chemical groupings to add or remove hydrogen atoms. 2. Transferases Transfer functional groups between donor and acceptor molecules. Kinases are specialized transferases that regulate metabolism by transferring phosphate from ATP to other molecules. 3. Hydrolases Add water across a bond, hydrolyzing it. 4. Lyases Add water, ammonia or carbon dioxide across double bonds, or remove these elements to produce double bonds. 5. Isomerases Carry out many kinds of isomerization: L to D isomerizations, mutase reactions (shifts of chemical groups) and others. 6. Ligases Catalyze reactions in which two chemical groups are joined (or ligated) using ATP.

11. 1.Addition or removal of water a.Hydrolases - these include esterases, carbohydrases, nucleases, deaminases, amidases, and proteases b.Hydrases such as fumarase, enolase, aconitase and carbonic anhydrase 2.Transfer of electrons a.Oxidases b.Dehydrogenases 3.Transfer of a radical a.Transglycosidases - of monosaccharides b.Transphosphorylases and phosphomutases - of a phosphate group c.Transaminases - of amino group d.Transmethylases - of a methyl group e.Transacetylases - of an acetyl group 4.Splitting or forming a C-C bond a.Desmolases 5.Changing geometry or structure of a molecule a.Isomerases 6.Joining two molecules through hydrolysis of pyrophosphate bond in ATP or other triphosphate a.Ligases

12. Oxidoreductases--catalyze redox reactions Usually require a coenzyme Ethanol + NAD+ Acetaldehyde + NADH + H+ Enzymes receive “common” names reflecting their function, either in the forward or reverse direction. The enzyme for this reaction is called Alcohol Dehydrogenase

13. Transferases-transfer functional groups Kinases transfer phosphates from ATP (or GTP) E.g Hexokinase: Glucose + ATP glc-6-P + ADP Hydrolases catalyze hydrolytic cleavages Proteases are hydrolases

14. Lyases catalyze group elimination to form double bonds e.g. Enolase (glycolysis) 2-Phosphoglycerate  H2O + phosphoenolpyruvate Isomerases--duh, interconvert isomers e.g. phosphoglucose isomerase Glucose-6-phosphate  Fructose-6-phosphate

15. Ligases--join to substrates together at the expense of ATP e.g. DNA Ligase Joins Okazaki fragments during DNA replication Some bacterial ligases substitute NAD+ as the energy source.

16. Coenzymes • Enzymes often require the participation of other small molecules to carry out a particular reaction. • These small molecules, called coenzymes, are metabolic derivatives of vitamins. • Vitamins are nutrients required in small amounts by organisms. Vitamin deficiencies usually present as metabolic disorders, e.g. scurvy

17. Table 13-1 The Common Coenzymes.

18. Table 13-2 Vitamins That Are Coenzyme Precursors. Page 464

19. Figure 13-2 The structures and reaction of nicotinamide-adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+). Page 461

20. Figure 13-4 Structures of nicotinamide and nicotinic acid. Page 464

21. Enzyme Activities Are Regulated at Various Levels • Transcription • Processing • Translation • Post-translational modification • Transient modification (e.g. phosphorylation) • Allosteric Effectors

22. Figure 13-5 The rate of the reaction catalyzed by ATCase as a function of aspartate concentration. Page 465

23. Figure 13-6 Schematic representation of the pyrimidine biosynthesis pathway. Page 466

24. Figure 13-7a X-Ray structure of ATCase. (a) (left) T-state ATCase along the protein’s molecular threefold axis of symmetry; (right) R-state ATCase along the protein’s molecular threefold axis of symmetry. Page 467

25. Figure 13-7b X-Ray structure of ATCase. (b) (left) T-state ATCase along the protein’s molecular twofold axis of symmetry; (right) R-state ATCase along the protein’s molecular twofold axis of symmetry. Page 467

26. Figure 13-8 Comparison of the polypeptide backbones of the ATCase catalytic subunit in the T state (orange) and the R state (blue). Page 468

27. Figure 13-9 Schematic diagram indicating the tertiary and quaternary conformational changes in two vertically interacting catalytic ATCase subunits. Page 469

30. Styer p.277

31. Stryer p. 278