2 amino acids and proteins lecture 2

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Principle of Biochemistry 2-Amino Acids and Proteins Course code: HFB324 Credit hours: 3 hours Dr. Siham Gritly 1 Dr. Siham Gritly
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  • 1.Principle of Biochemistry2-Amino Acids and Proteins Course code: HFB324 Credit hours: 3 hours Dr. Siham GritlyDr. Siham Gritly 1

2. Terms should be learned Protein; molecule consisting of one or morepolypeptide chains amino acid; an amino group and a carboxylic acidgroup attached to an alpha carbon (-C); ahydrogen and a small organic group (e.g., H, CH3, CH2OH), called an R-group, are also attachedto the -C Amphoteric; organic substance that acts as both anacid and a base chiral compound; molecule that cannot besuperimposed on its mirror imageDr. Siham Gritly 2 3. Enantiomers; two organic compounds that areare mirror images; these compounds containone or more chiral carbons L-amino acid; stereoisomeric form of aminoacids found in proteins N-terminus; (of a protein) the free amino end peptide bond; linkage between the aminogroup of one amino acid and the carboxylgroup of another amino acid peptide or polypeptide; a polymer chain ofthree or more amino acidsDr. Siham Gritly3 4. R-group; (of an amino acid) one of twenty (ormore) different organic groups bonded to thealpha carbon Stereoisomers; molecules with the samechemical formulae; they differ only in the way thedifferent attached groups are oriented in space Zwitterions; ion with a positive and a negativecharge Chirality describes the ability of a molecule torotate the plane of polarized light either to theright (dextrorotatory) or to the left (levorotatory Dr. Siham Gritly 4 5. Composition and nature of proteins; Proteins are complex organic compound foundin animal and plant tissues. The protein molecules are nitrogen-containingamino acids, in addition tocarbon, oxygen, and hydrogen. some of which are essential in the sense thathumans cannot make them internallyDr. Siham Gritly5 6. Protein functions 1-Structural function -Structural function Component of all cell membranes Component of cytoplasm "cytoskeleton" Component of movement or contractilestructures, such as muscle, Component of hair, nails horns, etc. (Keratinis the main protein of these substances) Dr. Siham Gritly 6 7. Protein functions 2-Metabolic functions 1-enzymatic function Most specialized proteins with catalyticactivity. All chemical reactions of organic biomoleculesin cells are catalyzed by enzymes Enzymes mainly consist of proteins. Dr. Siham Gritly7 8. 2-hormones (Regulatory Proteins) Help regulate cellular or physiological activity. The cellular response to many hormonalsignals is often mediated by a class of GTP-binding proteins called G proteins.Dr. Siham Gritly8 9. G proteins are important signal transductionmolecules in cells transmitting chemical signals originating fromoutside a cell into the inside of the cell. G proteins activity is regulated by factors thatcontrol their ability to bind to and hydrolyzeguanosine triphosphate (GTP) to guanosinediphosphate (GDP).Dr. Siham Gritly 9 10. 3-Immune function (Defense Proteins) Defend organisms against invasion by otherspecies or protect them Immunoglobulin or antibodies, are made bythe lymphocytes of vertebrates and canrecognize & precipitate or neutralize invadingbacteria Fibrinogen and thrombin are blood clottingproteins Dr. Siham Gritly10 11. 4-Acid base balance buffering agent Buffers ; are compounds that recover or (improve) achange in pH that occur in response to the addition ofalkali or acid to the solution or; A Buffers aresubstances that can bind protons Intracellular fluids; protein have the most bufferingeffect due to its high concentration in the blood. Less concentration of protein such as albumin in bloodcauses osmotic pressure in blood plasma decrease andthus fluid leak out into interstitial spaces causing edemaor swellingDr. Siham Gritly 11 12. edema or swelling Dr. Siham Gritly 12 13. Protein molecules possess basic and acidic groups(Amphoteric molecules )which act as H+acceptors or donors respectively if H+ is added orremoved. A solution with a high hydrogen ionconcentration has a low pH and is therefore moreacidic, whereas a solution with a low hydrogen ionconcentration has a high pH and is more alkaline Dr. Siham Gritly13 14. Protein buffer: COOH (acid) of amino acidcan lose H+ (COO-) NH2 (amine) of amino acid can gain H+(NH3+) (buffering effect)Dr. Siham GritlyLysine structure 14 15. 5-transport Bind and carry molecules or ions to organs inthe blood plasma. Lipoproteins in blood plasma carries lipidsfrom the live to other organs Dr. Siham Gritly 15 16. 6-Energy sources any amounts above the needed amino acids forsynthesis of tissues are metabolized and degraded. *The amino group of amino acid is converted tourea in the liver and excreted in urine throughurea cycle. *carboxylic group of amino acids are convertedto glucose and enter glycolysis pathway forenergy production.Dr. Siham Gritly 16 17. 7-Nutrient and Storage Proteins Seeds of many plants store nutrient proteinsrequired for the growth of the germinatingseedlings. Ovalbumin, the major protein of eggwhite, and casein the major protein of milk areexamples of nutrient proteins Dr. Siham Gritly 17 18. Denaturation of proteins Denaturation is the breakdown of all covalentbonds causing change in shape and thus loss offunction. Denaturation is due to -pH -temperature -salt concentration alcohol heavy metalsDr. Siham Gritly 18 19. Protein structureEach protein has a unique shape or conformation. all proteinsare composed exclusively of subunits of amino acids, which join together in long chains called polypeptides that fold or coil intothe unique shape of the functional protein Dr. Siham Gritly 19 20. 1-Primary structure of proteinsamino acids sequences The primary structure of a protein simplyconsists of its linear sequence of amino acids;for example, "alanine-glycine-tryptophan-serine-glutamate-asparagine-glycine-lysine- Dr. Siham Gritly 20 21. 2-Secondary structure As peptide bonds are formed, aligning theamino acids, hydrogen bonds form betweendifferent amino acids in the chain. This bonding coils the polypeptide into thesecondary structure of the protein, mostcommonly the alpha helix, The -helix coils at every 4th amino acid. Dr. Siham Gritly 21 22. 2-Secondary structureThe -helix coils of proteinDr. Siham Gritly 22 23. Pleated Proteinthe polypeptide have portions that lie parallel to each other (held by hydrogenbonds) instead of in the alpha helix, in which the amino acids hydrogen bonds form a pleated structure. Fibrous proteins have significant pleated structuresDr. Siham Gritly 23 24. 3-Tertiary Structure of protein the side chains (the R groups) of amino acids may foldindependently into a functional unit called the domain. Domains are connected by the rest of the polypeptide. The folding of a protein into its domains is related tothe hydrophilic or hydrophobic properties of its aminoacids. Domain formation is part of the tertiary structure orproteins. globular shape (globulin) Dr. Siham Gritly 24 25. Tertiary Structure of protein Dr. Siham Gritly 25 26. 5 kind of bonds stabilize tertiary structure 1-van der Waals interaction (betweenneighboring atoms) Van der Waals forcesinclude attractions and repulsions betweenatoms, molecules, and surfaces 2-H-bonds within the chains or between chainsDr. Siham Gritly 26 27. 3-hydrophobic interactions (between nonpolar) 4-ionic interactions (between oppositelycharged groups) 5-disulphide linkages, the SH groups of twoneighboring cysteines form s=s bond knownas disulphide linkage. (covalent bond) Dr. Siham Gritly 27 28. Amino acid Cysteine disulphide linkagescomposed of two cysteines linked by a disulfide bond Amino acid Cysteinetwo cysteines linked by a disulfide bondDr. Siham Gritly 28 29. 4-Quaternary Protein Structurethe structure formed by several protein molecules (polypeptidechains), usually called protein subunits If two or more polypeptide chains join inaggregate, they form a quaternarystructure, such as in the proteinmolecule, hemoglobin. Often quaternary proteins are complexed witha different molecule, often a mineral.Hemoglobin contains iron, for example.Dr. Siham Gritly 29 30. 4-Quaternary Protein StructureHaemoglobin structure Dr. Siham Gritly 30 31. Amino acidthe building blockof proteins Dr. Siham Gritly 31 32. Amino AcidGeneral structure of amino acidThe carbon atom next to the carboxyl group is called the carbon and amino acids with a side-chain bonded to this carbonare referred to as alpha amino acids. These are the most common form found in nature. Lysine structure Dr. Siham Gritly 32 33. Amino acids Amino acids contain Carbon,Hydrogen, Oxygen, Nitrogen, and sometimes Sulfur Amino acids have two function groups (both of which aretypically in the ionized form) 1- NH2 Amino functional group 2-COOH Carboxyl functional group Both functional groups attach to a specific carbon, thealpha carbon, of the carbon chain. The third bonding siteof the alpha carbon is typically Hydrogen. Dr. Siham Gritly 33 34. The alpha carbon will have at its fourthbonding site a side chain, or R group whichgives the amino acid its unique structure andproperties. There are 20 + different amino acids inprotein. All have a common structure exceptfor the R group. Dr. Siham Gritly 34 35. Some amino acids have R groups that are polar(hydrophilic), interact with water at physiological pH(O, N) some R groups are nonpolar (and hydrophobic C, H), some have acidic side chains pKa < the physiologicalpH 7.4. (generally with a negative charge) and some arebasic pKa > the physiological pH 7.4 pKa acid-ionization constant or acidity constant measure of the strength of an acid in solution Dr. Siham Gritly 35 36. Some with Amino Acids with Aliphatic R-Groups nonpolar and hydrophobic(Hydrophobicity increases with increasingnumber of C atoms in the hydrocarbon chain) Aromatic Amino Acids with benzene ring arerelatively nonpolar. aromatic amino acidsabsorb ultraviolet light.Dr. Siham Gritly36 37. Amino acids are joined together by adehydration synthesis of amino/carboxylgroups forming a peptide bond.Dr. Siham Gritly37 38. -Amino Acids structure Found in ProteinsBackbone of the amino acids is red, R-groups are blackreference; Michael W King, PhD | 9962012 themedicalbiochemistrypage.org, LLC| info @ themedicalbiochemistrypage.org pK1 pK R AminopK2Q AcidSymbolStructure*(COOH) (NH2) Group Amino Acids with Aliphatic R-Groups nonpolar and hydrophobic (C )GlycineGly G2.49.8Alanine Ala A 2.49.9 Valine Val V 2.29.7Dr. Siham Gritly 38 39. -Amino Acids Found in ProteinsBackbone of the amino acids is red, R-groups are blackreference; Michael W King, PhD | 9962012 themedicalbiochemistrypage.org, LLC| info @ themedicalbiochemistrypage.orgLeucin Leu 2.39.7eLIsoleuci Ile 2.39.8 ne INon-Aromatic Amino Acids with Hydroxyl R-Groups Ser Serine 2.29.2 13SDr. Siham Gritly 39 40. -Amino Acids Found in ProteinsBackbone of the amino acids is red, R-groups are blackreference; Michael W King, PhD | 9962012 themedicalbiochemistrypage.org, LLC | info @ themedicalbiochemistrypage.org Threonine Thr T 2.1 9.113 Amino Acids with Sulfur-Containing R-Groupsnonpolar and hydrophobic Cysteine Cys C1.9 10.88.3MethionineMet M2.19.3 Acidic Amino Acids and their AmidesAcidic Amino Acids and their Amides Acidic amino acids are polar and negatively charged at physiological pH. Both acidic amino acids have a second carboxyl grouphydrophilicAspartic Acid Asp D2.09.93.9 Dr. Siham Gritly40 41. -Amino Acids Found in ProteinsBackbone of the amino acids is red, R-groups are blackreference; Michael W King, PhD | 9962012 themedicalbiochemistrypage.org, LLC| info @ themedicalbiochemistrypage.orgAsparaginAsn N2.18.8 eGlutamic Glu E 2.19.5 4.1AcidGlutamine Gln Q2.29.1Dr. Siham Gritly 41 42. -Amino Acids Found in ProteinsBackbone of the amino acids is red, R-groups are blackreference; Michael W King, PhD | 9962012 themedicalbiochemistrypage.org, LLC| info @ themedicalbiochemistrypage.orgBasic amino acidsArginine Arg R1.8 9.0 12.5 Lysine Lys K 2.2 9.2 10.8Histidine His H 1.8 9.26.0 Dr. Siham Gritly42 43. -Amino Acids Found in ProteinsBackbone of the amino acids is red, R-groups are black reference; Michael W King, PhD | 9962012 themedicalbiochemistrypage.org, LLC | info @themedicalbiochemistrypage.orgAmino Acids with Aromatic Ringscyclic side groups (benzene ring)Phenylalanine Phe F 2.29.2TyrosineTyr Y 2.29.1 10.1 Tryptophan Trp W 2.49.4 Dr. Siham Gritly 43 44. -Amino Acids Found in Proteins Backbone of the amino acids is red, R-groups are blackreference; Michael W King, PhD | 9962012 themedicalbiochemistrypage.org, LLC | info @ themedicalbiochemistrypage.orgImino AcidsProline Pro P 2.010.6Dr. Siham Gritly44 45. The amino acids found in proteins have a common stereochemistryOptical Properties of the Amino AcidsIsomerism In organic chemistry, this stereochemistry isreferred to as L (for levo, meaning left). A tetrahedral carbon atom with 4 distinctconstituents is said to be chiral Chirality is the ability of a molecule to rotatethe plane of polarized light either to the right(dextrorotatory) or to the left (levorotatory).Dr. Siham Gritly 45 46. All of the amino acids in proteins exhibit thesame steric configuration as L-glyceraldehyde the amino group is always to the left side of thealpha carbon, Thus, the amino acids found inproteins are L-alpha amino acids D-amino acids are never found in proteins,although they exist in nature. D-amino acids areoften found in polypetide antibiotics Dr. Siham Gritly 46 47. Acid-Base Properties of the AminoAcids The -COOH and -NH2 groups in amino acids arecapable of ionizing (as are the acidic and basic R-groups of the amino acids). As a result of theirionizability the following ionic equilibriumreactions may be written: R-COOH R-COO + H+ R-NH3+ R-NH2 + H+ The equilibrium reactions, demonstrate thatamino acids contain at least two weakly acidicgroups. Dr. Siham Gritly 47 48. the carboxyl group is stronger acid than the amino group. At physiological pH (around 7.4) the carboxyl group will be unprotonated and the amino group will be protonated.An amino acid with no ionizable R-group would be electricallyneutral at this pH. This species is termed a zwitterion.An amino acid in its (1) un-ionized and (2) zwitterionicforms Dr. Siham Gritly 48 49. Carboxylic acid groups (CO2H) can bedeprotonated to become negativecarboxylates (CO2 ), and -amino groups (NH2) can be protonatedto become positive -ammonium groups(+NH3).Dr. Siham Gritly49 50. Amino acid and peptide linkageDr. Siham Gritly 50 51. Peptide linkageamino acids are the structural units of the body protein. They are all amino-carboxylic acids. All amino acids join together to form Peptide link. Peptide bond is formed by condensation reaction and broken by hydrolysis Dr. Siham Gritly51 52. Peptide linkageAll peptides and polypeptides are polymers of -amino acids *A protein starts as a chain of amino acids,called a polypeptide *Amino acids are joined by the peptide bond,via dehydration synthesis to form thepolypeptide *The polypeptide chain is referred to as theprimary structure of the protein.Dr. Siham Gritly 52 53. *The specific amino acids in the polypeptidechain will determine its configuration, orshape, and therefore, its function. one amino acid substitution in the bondingsequence of a polypeptide can alter the finalproteins shape and ability to functionDr. Siham Gritly53 54. Essential and non essential amino acids EssentialNonessentialIsoleucine AlanineLeucineAsparagineLysine Aspartic AcidMethionine Cysteine*PhenylalanineGlutamic AcidThreonineGlutamine*Tryptophan Glycine* Dr. Siham Gritly54 55. Essential NonessentialValine Proline* Selenocysteine* Serine* Tyrosine* Arginine* Histidine* Ornithine* Taurine* Dr. Siham Gritly 55 56. *Nonessential amino acids can be synthesizedthrough a process called transamination. *Transamination involves the transfer of anamino acid group from 1 amino acid to acarbon skeleton to form a new amino acid.Dr. Siham Gritly 56 57. Dr. Siham Gritly 57 58. Amino acids can be transaminated to formalanine from pyruvate *the alanine is transported to the liver asprimary substrate for gluconeogenesis *this process known as glucose-alanine cycle Dr. Siham Gritly58 59. Diseases associated with protein Sickle Cell Comparedwith Normal Red Blood Cell Dr. Siham Gritly59 60. sickle-cell anemia: a hereditary form of anemia characterized by abnormal sickle- or crescent-shapedred blood cells. Sickled cells interfere with oxygentransport and blood flow. Symptoms are precipitated by dehydration andinsufficient oxygen (as may occur at high altitudes) andinclude hemolytic anemia (red blood cells burst), fever,and severe pain in the joints and abdomen. gene expression: the process by which a cell converts the genetic code into RNA and protein. Dr. Siham Gritly60 61. Protein-Energy Malnutrition Dr. Siham Gritly 61 62. Adult Bone Loss (Osteoporosis Cancer Heart diseaseDr. Siham Gritly 62 63. Protein synthesis *For synthesis of protein all amino acids should bepresent or available at the same time (essential aminoacids). Synthesis or building of body proteinscontrolled by genetic material found in every cell. *the genetic material found in the nucleus of the cellis Deoxyribose Nucleic Acid (DNA) *the material DNA is used for synthesis of RiboseNucleic Acids (RNA). *there are different forms of RNA, such as mRNAwhich carries information to the cytoplasm where theprotein are synthesized. Dr. Siham Gritly63 64. *DNA & RNA are composed of ribose(pentose sugar) or deoxyribose, phosphoricacid and nitrogenous base (purine andpyrimidine) *in cytoplasma RNA moleculs tRNA direct theamino acids to correct position with the mRNAto built peptide chain and thus formation ofbody proteins. The coming lectures the discussion will be in more details Dr. Siham Gritly64 65. This process of messenger RNA being madefrom a template of DNA is known astranscription. This process of messenger RNA directing thesequence of amino acids and synthesis ofproteins is known as translation.Dr. Siham Gritly65 66. Protein break down (catabolism) *any amounts above the needed amino acidsfor synthesis of tissues are metabolized. *amino acids have both amino group andcarboxylic group. The amino group of aminoacid is converted to urea in the liver andexcreted in urine through urea cycle. *carboxylic group of amino acids areconverted to glucose and enter glycolysispathway for energy.Dr. Siham Gritly 66 67. Lab technique for studying protein purification,structure and function Proteins may be purified from other cellularcomponents using a variety of techniques; such as ultracentrifugation, precipitation, electrophoresis, and chromatography; Methods commonly used to study protein structure andfunction include; immunohistochemistry, site-directed mutagenesis, nuclear magnetic resonance mass spectrometryDr. Siham Gritly 67 68. References Murry K. Robert, Granner K. daryl, Mayes A. peter, RodwellW. Victor (1999). Harpers Biochemistry. Appleton and Lange ,twenty fifth edition Heymsfield, SB.; Olafson RP.; Kutner MH. and Nixon DW.1979. A radiographic method of quantifying protein-calorieunder nutrition American Journal of Clinical Nutrition,32: 693-702 Chang, Raymond (2007). Chemistry, Ninth Edition. McGraw-Hill. pp. 52. Sareen S. Gropper, Jack L.Smithh and James L. Groff; 2007.advanced Nutrition and Human Metabolism, fifth ed.Wadsworth CENGAGE learning Dr. Siham Gritly 68 69. Michael W King, PhD | 19962012 themedicalbiochemistrypage.org, LLC | [email protected] themedicalbiochemistrypage.org D. Voet, J. G. Voet, Biochemistry, second edition ed., John Wiley & Sons, New York, 1995 Sareen Gropper, Jack Smith and James Groff, Advanced Nutrition and HumanMetabolism, fifth ed. WADSWORTH Melvin H Williams 2010; Nutrition for Health, Fitness and Sport. 9th ed, McGrawHill Heymsfield, SB.; Baumgartner N.; Richard and Sheau-Fang P. 1999. ModernNutrition in Health and Disease; Shils E Maurice, Olson A. James, ShikeMoshe and Ross A. Catharine eds. 9th edition Guyton, C. Arthur. 1985. Textbook of Medical Physiology. 6th edition, W.B.Company Dr. Siham Gritly 69