CHAPTER 21: Amino Acids, Proteins, & Enzymes General, Organic, & Biological Chemistry
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CHAPTER 21: Amino Acids, Proteins, & Enzymes General, Organic, & Biological Chemistry Janice Gorzynski Smith CHAPTER 21: Amino Acids, Proteins, Enzymes Learning Objectives: The 20 common, naturally occurring Amino Acids stereochemistry acid/base chemistry Peptides Formation N & C terminals Proteins Primary, Secondary, Tertiary, Quaternary structure Hydrolysis and denaturation Enzymes Catalysis Inhibitors Zymogens CH 21 Homework: End of Chapter problems: 32, 36, 38, 42, 48, 50, 52, 62, 64, 68, 70, 74, Smith, Janice Gorzynski. General, Organic, 77, 81, 93, 94 & Biological Chemistry 2nd Ed. 2 Amino Acids Definition All amino acids contain two functional groups—an amino group (NH2) and a carboxyl group (COOH). Amino acids differ in the R group bonded to the α carbon Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 3 Amino Acids At isoelectric pH • The isoelectric point for amino acids is about 6, this is the pH at which the amino acid exists as a neutral molecule • The pKa of the amine group is usually about 9-11 • The pKa of the carboxylic acid group is usually about 2-3 Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 4 Amino Acids Acid/Base Chemistry Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 5 Amino Acids Stereochemistry • Carbohydrates: naturally occurring isomer is the Disomer (OH group on right in a Fischer projection) • Amino Acids: most naturally occurring isomers are the Lisomer (NH3 group on the left in a Fischer projection) Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 6 The 20 common & naturally occurring amino acids in humans. Essential Amino Acids: Isoleucine (Ile) Leucine (Leu) Methionine (Met) Phenylalanine (Phe) Threonine (Thr) Tryptophan (Trp) Valine (Val) Arginine (Arg) Histidine (His) Lysine (Lys) 7 Peptides Definition •Peptides and proteins are formed when amino acids are joined together by amide bonds. •A dipeptide has two amino acids joined together by one amide bond. •The amide bond is called a peptide bond. •Polypeptides have many amino acids, while proteins have more than 40 amino acids. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 8 Peptides Amide Bond Formation Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 9 Peptides Amide Bond Formation Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 10 Peptides N & C Terminal Amino Acids •The amino acid with the free –NH3+ group is the N-terminal amino acid and is written on the left. •The amino acid with the free –COO− group is the C-terminal amino acid and is written on the right. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 11 Peptides/Prote in Insulin Gly-Ile-Val-Glu-Gln-Cys-Cys-Thr-Ser-Ile-Cys-Ser-Leu-Tyr-Gln-Leu-Glu-Asn-Tyr-Cys-R Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val-Cys-GlyGlu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Thr-R’ Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 12 Proteins Primary Structure The primary structure of a protein is the sequence of amino acids joined together by peptide bonds. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 13 Proteins Secondary Structure •The secondary structure is the 3D arrangement of localized regions of a protein. •These regions arise due to hydrogen bonding between the N—H group of one amide with the C═O group of another. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 14 Proteins Secondary Structure Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 15 Proteins Tertiary Structure The tertiary structure is the 3D shape adopted by the entire peptide chain: • Maximize Hydrogen bonding with water (hydrophilic) • Stabilize non-polar sidechains by london dispersion forces (hydrophobic) • Polar functional groups H-bond with each other • Charged sidechains attracted through electrostatic interactions • Disulfide bonds form Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 16 Proteins Tertiary Structure Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 17 Proteins Quaternary Structure The quaternary structure of the protein is the shape adopted when two or more folded poly-peptide chains come together into one complex. Ex: Potassium Channel: Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 18 Proteins Quaternary Structure Hemoglobin Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 19 Proteins Quaternary Structure Hemoglobin Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 20 Proteins 1°, 2°, 3°, 4° Structure Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 21 Proteins Peptide Hydrolysis Protein hydrolysis involves breaking the peptide bonds by treatment with aqueous acid, base, or certain enzymes: Pepsin (gastric juices), Trypsin and Chymotrypsin (intestines) Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 22 Proteins Peptide Denaturation Denaturation is the process of altering the shape of a protein without breaking the amide bonds that form the primary structure: heat, acid, base, or agitation Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 23 Enzymes Definition Enzymes are proteins that serve as biological catalysts for reactions in all living organisms. • They increase the rate of a reaction (106 to 1012 times faster), but are unchanged themselves. • Enzymes are very specific; each enzyme catalyzes a certain reaction or type of reaction only. • The names of most enzymes end with the suffix “-ase” like peptidase, lipase, and hydrolase • A cofactor is a metal ion or an organic molecule needed for an enzyme-catalyzed reaction to occur. Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 24 Enzymes Function http://leavingbio.net/enzymes.htm 25 Enzymes Conformational Changes Upon Binding 26 http://plantcellbiology.masters.grkraj.org/html/Plant_Cell_Biochemistry_And_Metabolism1-Proteins_And_Enzymes.htm Enzymes Inhibition 27 http://o.quizlet.com/i/WRLW8kdWLDOY1YZbEdKgyA_m.jpg Enzymes HIV Protease Inhibitor Protease inhibitors are designed to mimic a peptide linkage (-NH-CO-) but replaces the linkage with a –CH2-CH(OH)- which binds to the active site but the protease cannot cleave a linkage so it stays bound. Saquinavir: 28 http://en.wikipedia.org/wiki/Discovery_and_development_of_HIV-protease_inhibitors Enzymes Lipoxygenase Inhibitor Zileuton is an asthma maintenance medication that inhibits 5-lipoxygenase, therefore, inhibiting leukotriene formation. 29 http://en.wikipedia.org/wiki/Zileuton Enzymes Differences in Binding Sites Superoxide Dismutase: SOD Hydrophobic Binding Pocket Superoxide Reductase: SOR Hydrophilic Binding Pocket Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 30 Mechanistic Differences: SOR vs SOD Enzymes OH OAsp FeIII O2 - NHis OH NHis O2- H+ O2 NHis SOD Mechanism OH2 NHis OAsp FeIII OAsp FeII NHis NHis NHis NHis OH2 HOOH H+ NHis 2H+ OAsp FeII NHis NHis O2 H2O SOR Mechanism - O2NHis * O2- hydrogen bonds to residues in secondary coordination sphere, positioning it near Fe(II), Smith, Janice Gorzynski. General, Organic, & Biological Chemistry 2nd Ed. 31 Enzymes Zymogens Smith, Janice Gorzynski. 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