Amino Acids, Peptides, & Proteins Part 1 PDF

Chapter 3 Amino Acids, Peptides, and Proteins PART 1 3.1 Amino Acids  Principle 1 (2 of 2) In every living organism, proteins are constructed from a common set of 20 amino acids. Each amino acid has a side chain with distinctive chemical properties. Amino acids may be regarded as...

Chapter 3 Amino Acids, Peptides, and Proteins PART 1 3.1 Amino Acids  Principle 1 (2 of 2) In every living organism, proteins are constructed from a common set of 20 amino acids. Each amino acid has a side chain with distinctive chemical properties. Amino acids may be regarded as the Loading… alphabet in which the language of protein structure is written.  Functions of Proteins Biological catalyst Transport Structural support Functions of Proteins Loading… Immune response Biological regulation  Amino Acids Share Common Structural Features α carbon and four substituents α carbon is the chiral center tetrahedral  Amino Acid Substituents four substituents: – a carboxyl group – an amino group – a hydrogen atom – an R group (a side chain unique to each amino acid) glycine has a second hydrogen atom instead of an R group  The Amino Acid Residues in Proteins are L Stereoisomers two possible stereoisomers = enantiomers optically active D, L system specifies absolute configuration  Amino Acids Can Be Classified by R Group Five main classes: 1. nonpolar, aliphatic (7) 2. aromatic (3) 3. polar, uncharged (5) 4. positively charged (3) 5. negatively charged (2) Nonpolar, aliphatic R groups the hydrophobic effect stabilizes protein structure Loading… Aromatic R Groups R groups absorb UV light at 270–280 nm can contribute to the hydrophobic effect UV light absorption by aromatic amino acids  Lambert-Beer law 280 nm Aromatic amino acids Absorption of UV light is a measure of amino acid concentration in solution Polar, Uncharged R Groups R groups can form hydrogen bonds cysteine can form disulfide bonds Oxidation of two cysteine molecules form disulfide bond Oxidation Reduction Reversible reaction  Two types of disulfide bonds Intra-molecular Insulin molecule disulfide bond Inter-molecular disulfide bond Positively Charged R Groups have significant positive charge at pH 7.0 ? Negatively Charged R Groups have a net negative charge at pH 7.0 Uncommon Amino Acids Also Have Important Functions modifications of common amino acids: – modified after protein synthesis (e.g., 4-hydroxyproline, found in collagen) – modified during protein synthesis (e.g., pyrrolysine, contributes to methane biosynthesis) – modified transiently to change protein’s function (e.g., phosphorylation) free metabolites (e.g., ornithine, intermediate in arginine biosynthesis) Amino acid abbreviations and symbols For convenience, the names of all the standard amino acids are designated by either three letter abbreviations or by one letter symbol For most amino acids, the first three letters of their names represent the abbreviations Exceptions Isoleucine Asparagine Glutamine Tryptophan Amino acid acts as diprotic acid + 0 -1 1 pH changes charge on amino acids Amino Acids Can Act as Acids or Bases amino groups, carboxyl groups, and ionizable R groups = weak acids and bases zwitterion occurs at neutral pH Zwitterion predominates at neutral pH  Titration of Amino Acids cation ⇌ zwitterion ⇌ anion —COOH has an acidic pKa (pK1) —NH3+ has a basic pKa (pK2) the pH at which the net electric charge is zero is the isoelectric point (pI) Effect of the Chemical Environment on pKa α-carboxyl group is more acidic than in carboxylic acids α-amino group is less basic than in amines  Information from a Titration Curve quantitative measure of the pKa of each ionizing group regions of buffering power relationship between its net charge and the pH of the solution – isoelectric point, pI  Since all amino acids have common amino and carboxyl groups, they have similar pK1 and pK2values pK1 refers to pKa of COOH group & ranges between 1.8-2.4 Loading… pK2 refer to pKa of NH3+ group & ranges between 8.8-11.0 Since pK1 of all the amino acids fall in between pH 1.8 and 2.4, the carboxylic groups of all amino acids will be deprotonated (COO-) at pH higher than pH 2.4 and they all will carry negative charge. Similarly Since pK2 of all the amino acids fall in between pH 8.8 and 11.0, the amino groups of all amino acids will be protonated (NH3+) at pH lower than pH 8.8 and they all will carry positive charge.  Amino Acids as Buffers buffers prevent changes in pH close to the pKa glycine has two buffer regions: – centered around the pKa of the α- carboxyl group (pK1 = 2.34) – centered around the pKa of the α-amino buffer group (pK2 = 9.6) regions  Isoelectric Point, pI for amino acids without ionizable side chains, the isoelectric point (pI) is: pH = pI = net charge is zero (amino acid least soluble in water, does not migrate in electric field) pH > pI = net negative change pH < pI = net positive charge  Amino Acids Differ in Their Acid- Base Properties ionizable side chains: – have a pKa value – act as buffers – influence the pI of the amino acid – can be titrated (titration curve has 3 ionization steps) Titration of Amino Acids with an Ionizable R Group Positively Charged R Groups have significant positive charge at pH 7.0 ? 3.2 Peptides and Proteins  Principle 2 (2 of 3) In proteins, amino acids are joined in characteristic linear sequences through a common amide linkage, the peptide bond. The amino acid sequence of a protein constitutes its primary structure, a first level we will introduce within the broader complexities of protein structure.  Peptides Are Chains of Amino Acids peptide bond: – covalent – formed through condensation – broken through hydrolysis  Peptide Types by the Number dipeptide = 2 amino acids, 1 peptide bond tripeptide = 3 amino acids, 2 peptide bonds oligopeptide = a few amino acids polypeptide = many amino acids, molecular weight < 10 kDa protein = thousands of amino acids, molecular weight > 10 kDa  Peptide Terminals numbering (and naming) starts from the amino-terminal residue (N-terminal) N-terminal C-terminal  Naming Peptides full amino acid names: serylglycyltyrosylalanylleucine three-letter code abbreviations: Ser–Gly–Tyr–Ala–Leu one-letter code abbreviation: SGYAL  Peptides Can Be Distinguished by Their Ionization Behavior ionizable groups in peptides: – one free α-amino group – one free α- carboxyl group – some R groups Biologically Active Peptides and Polypeptides Occur in a Vast Range of Sizes and Compositions Number of length of naturally Table Protein 3-2 Molecular Molecularweight Data on Number of Some polypeptide residuesProteinschains occurring peptides Cytochrome c (human) 12,400 104 1 = 2 to many Myoglobin (equine 16,700 153 1 thousands of heart) amino acid Chymotrypsin (bovine pancreas) 25,200 241 3 residues Hemoglobin (human) 64,500 574 4 Hexokinase (yeast) 107,900 972 2 RNS polymerase (E. 450,00 4,158 5 coli) Glutamine synthetase 619,000 5,628 12 (E. coli) Titin (human) 2,993,000 26,926 1  Amino Acid Composition of Proteins Table 3-3 Amino Acid Composition of Two Proteins amino acid Bovine cytochrome c: Number of residues per Bovine cytochrome c: Bovine chymotrypsinogen: Bovine chymotrypsinogen: Amino Acid molecule percentage of total Number of residues per molecule Percentage of total composition Ala 6 6 22 9 is highly Arg Asn 2 5 2 5 4 14 1.6 5.7 variable Asp 3 3 9 3.7 Cys 2 2 10 4 Gln 3 3 10 4 Glu 9 9 5 2 Gly 14 13 23 9.4 His 3 3 2 0.8 Ile 6 6 10 4 Leu 6 6 19 7.8 Lys 18 17 14 5.7 Met 2 2 2 0.8 Phe 4 4 6 2.4 Pro 4 4 9 3.7 Ser 1 1 28 11.4 Thr 8 8 23 9.4 Trp 1 1 8 3.3 Tyr 4 4 4 1.6 Val 3 3 23 9.4  Estimating the Number of Amino Acid Residues number of residues = molecular weight/110 average molecular weight of amino acid = ~128 molecule of water removed to form peptide bond = 18 128 – 18 = 110  Some Proteins Contain Chemical Groups Other Than Amino Acids conjugated proteins = Table 3-4 Conjugated Proteins Class Prosthetic group Example contain permanently Lipoproteins Lipids β1-Lipoprotein of blood associated chemical (Fig. 17-2) components Glycoproteins Carbohydrates Immunoglobulin G (Fig. 5-20) – non–amino acid part Phosphoproteins Phosphate groups Glycogen phosphorylase = prosthetic group (Fig. 6-39) Hemoproteins Heme (iron porphyrin) Hemoglobin (Figs 5-8 to 5-11) lipoproteins contain lipids Flavoproteins Flavin nucleotides Succinate dehydrogenase (Fig. 19-9) Metallproteins Iron Ferritin (Box 16-1) glycoproteins contain Zinc Alcohol dehrogenase Calcium (Fig. 14-12) sugars Molybdenum Calmodulin (Fig. 12-17) Copper Dinitrogenase (Fig. 22-3) Complex IV (Fig. 19-12) metalloproteins contain specific metals  Some Proteins Contain Chemical Groups Other Than Amino Acids conjugated proteins = Table 3-4 Conjugated Proteins Class Prosthetic group Example contain permanently Lipoproteins Lipids β1-Lipoprotein of blood associated chemical (Fig. 17-2) components Glycoproteins Carbohydrates Immunoglobulin G (Fig. 5-20) – non–amino acid part Phosphoproteins Phosphate groups Glycogen phosphorylase = prosthetic group (Fig. 6-39) Hemoproteins Heme (iron porphyrin) Hemoglobin (Figs 5-8 to 5-11) lipoproteins contain lipids Flavoproteins Flavin nucleotides Succinate dehydrogenase (Fig. 19-9) Metallproteins Iron Ferritin (Box 16-1) glycoproteins contain Zinc Alcohol dehrogenase Calcium (Fig. 14-12) sugars Molybdenum Calmodulin (Fig. 12-17) Copper Dinitrogenase (Fig. 22-3) Complex IV (Fig. 19-12) metalloproteins contain specific metals