Amino acids and protein chemistry 1

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Dr.Ehab Aboueladab

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2. GENERAL STRUCTURE/FORMULA OF AMINO ACIDS1. -carbon bonded to an amino group, acarboxyl group, a hydrogen atom and aside-chain group. - Carbon2. The amino group bonded to the -carbonmakes all AAs for that matter as -aminoCOO- CarboxylHydrogenacids.3. R group determines the identity of thegroup| AA and the role or biologic property of the+H N- C H AA in a protein molecule. 34. Carbon atoms of the side chains are sequentially labeled as , , , , which| AminoR refer to carbons 3, 4, 5, and 6 respectively. Side chain group5. -carbon is a chiral or asymmetric carbon because there are 4 different groups attached to it. 7. At physiologic ph (7.4), the COOH group is6. All AAs except glycine have chiral deprotonated, forming the negatively charged carbons; glycine has 2 H atoms attachedcarboxylate ion ( -CO0-) and the amino group to the -carbon, hence a symmetric is protonated (-NH3+). molecule. 8. With each AA containing at least one amino7. The amino and carboxyl groupsand carboxylic acid group, amino acids are participate in chemical reactions, henceclassified as amphoteric substances and react constitute the functional groups of aminowith both acids and bases. acids and are unique to all amino acids. 3. D & L FORMS (ISOMERS) OF AMINO ACIDS1. Glyceraldehyde is used as a reference compound for D and L isomers of amino acids (similar to carbohydrates).2. In L-glyceraldehyde, the OH- group is on the left side of the molecule; in D-glyceraldehyde, the OH- group is on the right side.3. In L-amino acid as L-alanine, the amino group (NH3+) is on the left side with the carboxyl group at the top of the structure; in D-alanine, the amino group is on the right side with the carboxyl group at the top of the structure.4. In proteins, all of the AAs are in the L-isomer; hence by convention, all AAs are presumed to be in the L configuration unless specifically designated. 4. CLASSIFICATION OF AMINO ACIDS- based on the chemical properties of the side chainsGrp I. AAs with Non-polar or Hydrophobic Side Chains have the tendency to cluster away from H2O (or H2O-hating) Imino group1. Leucine have 4-carbon side chain; the purely ketogenic amino acid.2. Proline a. Its 3-carbon side chain is bonded to the nitrogen of its -amino group and to the -carbon, creating a cyclic or ring structure; this amino acid contains a secondaryrather than a primary amino group, hence an imino acid or a secondary amine. b. This substituted -amino group influences protein folding by forcing a bend in thepolypetide chain. 5. CLASSIFICATION OF AMINO ACIDSGrp I. AAs with Non-polar Side Chains alsothought of as oily or lipid-like.Alanine has a methyl group side chain. 6. CLASSIFICATION OF AMINO ACIDSGrp I. AAs with Non-polar Side Chains1. Methionine side chain contains a sulfur group, similar to cysteine2. Tryptophan side chain contains an indole ring; classified as a neutral amino acid. In Hartnups Disease, there is inability of the intestinal epithelial cells to absorb neutral amino acids like tryptophan excessive amount in the urine impaired synthesis of niacinamide.3. Phenylalanine hydrocarbon group is aromatic; i.e., contains a cyclic group similar to a benzene ring. 7. CLASSIFICATION OF AMINO ACIDSGrp 2. AAs with Neutral Polar Side Chains (Uncharged) participate in hydrogen bonding1. Glycine with very small side chain, hence it causes the least hindrance in a protein (i.e., it does not significantly impinge on the space occupied by other atoms or chemical groups); the simplest AA.2. Serine polar hydroxyl (OH-) group is bonded to aliphatic hydrocarbon groups.3. Asparagine & Glutamine with amide groups in their side chains. 8. CLASSIFICATION OF AMINO ACIDSGrp 2. AAs with Neutral Polar Side Chains (Uncharged)Threonine with 2 asymmetriccarbonsCysteine polar grp. consists of a SH (thiol) grp. which can react with other cysteine SH grps. to form disulfide bridges (-S-S-) or bonds in proteins.Tyrosine hydroxyl grp. is bonded toan aromatic hydrocarbon grp. 9. CLASSIFICATION OF AMINO ACIDSGrp 3. AAs with Carboxyl Groups in their Side Chains (Acidic)The carboxyl grp. (in addition to the one present in all AAs, hence dicarboxylic amino acids) makes these amino acids negatively charged. 10. CLASSIFICATION OF AMINO ACIDS Grp 4. AAs with Basic Side Chains positively charged1. Histidine side chain consists of an imidazole group2. Arginine side chain basic group (guanidino group) is bonded to an aliphatic hydrocarbon tail; the most basic amino acid.3. Lysine side chain amino group is attached to an aliphatic hydro- carbon tail 11. FORMATION OF THE PEPTIDE BOND Slide shows thepeptide bond (C-N)formed between thecarboxyl group ofvaline and the aminogroup of alanine toform a dipeptide, readas valylalanine, notalaninevaline. Again, each componentAA in the dipeptide iscalled a residue ormoiety. 12. PRIMARY STRUCTURE Refers to the linear sequence of aminoacids in a polypeptide chainLEU-GLY-THR-VAL-ARG-ASP-HIS VAL-HIS-ASP-LEU-GLY-ARG-THR1. Although these 2 peptides have the same number and kinds of amino acids, they have different sequence of amino acids and hence have different primary structure.2. The primary structure determines its 3-dimensional structure, properties and functions of a protein.3. This primary structure is determined from the genetic information encoded in DNA. 13. SECONDARY STRUCTURERefers to the hydrogen-bonded arrangement of the backbone of the polypeptide chain.1. There are 2 bonds within an AA with reasonably free rotation: a. bond bet. the -carbon and the aminonitrogen of the residue b. bond bet. the -carbon and thecarboxyl carbon of that residue.2. A peptide chain backbone can be visualizedas a series of playing cards, each cardrepresenting a planar peptide group.3. The cards are linked at opposite corners byswivels, representing the bonds about whichthere is a considerable rotation.4. The angles (phi) and (psi), frequentlycalled Ramachandran angles, are used todesignate rotation around the C-N (-carbonand amino nitrogen) and C-C (-carbon andcarboxyl carbon) bonds respectively.5. The side chains also play vital role indetermining the 3-dimensional shape of theprotein, but only the backbone is consideredin the secondary structure. 14. TERTIARY STRUCTURE OF PROTEINS1. Refers to the shape of the fully folded polypeptide chain, hence distant portions of the secondary structures are close together.2. Exemplified by the structure of MYOGLOBINa. Myoglobin is a compact structure consisting of a single polypeptide chain (153 AAs) and the prosthetic group heme-containing Fe.b. It consists of 8 helices (A to H) stabilized by hydrogen bonds and so are the AA side chains. 15. QUARTERNARY STRUCTURE OF PROTEINS1. Refers to the arrangement of 2 or more polypeptide chains or subunits with respect to one another to form a multisubunit molecule.2. Exemplified by the structure of HEMOGLOBIN a. Hemoglobin is a tetramer consisting of4 polypeptide chains:*2 -chains (blue color) each chainis 141 residues long*2 -chains (green color) each chain is 146 residues longb. The 2 -chains are identical; the 2 -chains are likewise identical.c. Hemoglobin has therefore this overall structure: 22.d. Buried in a crevice within each of the and -chains are the prosthetic groups hemes containing Fe+2. 16. DENATURATION OF PROTEINS1. Refers to the unfolding of the protein hence destruction of its native conformation, esp. of the secondary and tertiary structure.2. This is not accompanied by hydrolysis of the peptide bonds.3. Agents that cause denaturation: a. Heat causes vibrations disruptionof tertiary structure unfolding ordenaturation. b. Extremes of pH decreaseelectrostatic interactions thatmaintain native, active form denaturation. c. Chemical Agents: c1. Chaotropic urea and guanidinium salts c2. Detergents sodium didecyl sulfate (DDS) 17. PROTEIN DIGESTION AND AMINO ACID ABSORPTION 18. OVERVIEW OF DIGESTION OF DIETARY PROTEINS1. Proteins are too large to be absorbed, hence they must be first hydrolyzed to their constituent amino acids. Food2. Digestion occurs via the sequentialStomach action of proteolytic enzymes in the stomach, pancreas & small intestines.Protein HCl PepsinPancreas a. In the stomach, dietary proteins areconverted to polypeptides & somePolypeptidesfree amino acids by pepsin. HCO3- b. In the small intestines, trypsin,Trypsinchymotrypsin, elastase & carboxy- Chymotrypsinpeptidases A & B produce oligopep-Elastasetides in the presence of HCO3- (which CarboxypeptidasesSmallneutralizes the stomach acid &A&Bintestineraises the pH for activation of the Oligopeptideszymogens). c. Final digestion occurs via amino-Aminopeptidasespeptidases to produce free AAs and Bloodsmaller peptides like di- and Di- and tri- Di- and tri-tripeptides. peptidases Amino peptides acidsAmino3. Amino acids are then absorbed by the intestinal epithelial cells, brought to + acids the liver (via the portal system) forAmino metabolism or release into theacids general circulation. Intestinal epithelial cell 19. ACTIVATION OF THE GASTRIC AND PANCREATIC ZYMOGENS ProenzymesActive Enzymes H+ (parietal cells) PepsinogenPepsin Enteropeptidase Trypsinogen (enterokinase)Trypsin trypsin ChymotrypsinogenChymotrypsin ProelastasetrypsinElastase Procarboxypeptidase A & B trypsin Carboxypeptidae A & B1. The gastric and pancreatic zymogens involved in protein digestion are secreted in their inactive precursors or zymogen forms initially and then converted to their active forms.2. Pepsinogen, secreted by the chief cells of the stomach, is converted to pepsin via HCl (from gastric parietal cells) and autocatalytically by pepsin.3. Trypsinogen is converted to the active form trypsin by enteropeptidase (formerly enterokinase) from intestinal mucosal cells.4. Thereafter, trypsin cleaves the other pancreatic zymogens, producing their active forms.5. Trypsin is therefore the master or common activator