Protein Chemistry - First Lecture 2-10-2024.pdf
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Protein Chemistry Dr. Nancy Shahin Associate Professor of Biochemistry Faculty of Pharmacy, Cairo University Building A, 5th Floor (A503) [email protected] Protein Chemistry Part I 3 CHAPTER OUTLINE Protein: Structure and functions...
Protein Chemistry Dr. Nancy Shahin Associate Professor of Biochemistry Faculty of Pharmacy, Cairo University Building A, 5th Floor (A503) [email protected] Protein Chemistry Part I 3 CHAPTER OUTLINE Protein: Structure and functions Learning Objectives: ❖ By the end of this chapter, you should be able to : Recognize the structures of the 20 amino acids commonly found in proteins. Define the properties of their side chains and how these properties affect protein structure. Identify the different classes of amino acids and proteins. Recognize the structure of peptide bond. Describe the forces that determine how proteins fold. Identify the four levels of protein structure. Define protein denaturation. Proteins: The primary worker molecule in the body Transport- hemoglobin in blood, albumin Storage- ferritin in liver Immune response- antibodies Receptors- sense stimuli, e.g. in neurons Channels- control cell contents Structure- collagen in skin Enzymes- catalyze biochemical reactions Cell functions- multi-protein machines 6 Proteins are amino acid polymers 20 different amino acids: many combinations Proteins are made in the RIBOSOME RIBOSOME amino acids Proteins 7 L-Form Amino Acid Structure Carboxylic group - COO Amino group + H3 N C H H = Glycine R group CH3 = Alanine carbon Amino Carboxyl group group General structural formula of amino acids 9 Mirror Images of Amino Acid Mirror image Same chemical properties Stereo isomers Stereoisomers of Amino Acids All of the Amino Acids incorporated by organisms into proteins are in the L form Note: glycine is not chiral because its side chain is H. 11 Classification of amino acids Amino acids can be classified according to: 1. Structure of side chain (R): Aliphatic amino acids or Aromatic amino acids. 2. Polarity of side chain (R): (Polar or Non-Polar). 3. Nutritional requirement: (Essential or Non- Essential). 4. Metabolic fate: (Glucogenic, ketogenic, and Mixed (glucogenic and Ketogenic) amino acids. 13 Classification based on structure Aliphatic amino acids Aromatic amino acids Imino acid: proline Aliphatic, neutral Simple Branched-chain Aliphatic, neutral Alcoholic amino acids with OH groups Aliphatic, neutral Sulfur-containing amino acids polar nonpolar Aliphatic acidic amino acids and their amides Monoamino dicarboxylic acids Amino acids with amide group acidic neutral Aliphatic, neutral Amino acids with amide group Aliphatic basic amino acids Diamino monocarboxylic acids Guanido gp Aromatic basic amino acid Imidazole gp Aromatic amino acids Indole ring Nonpolar Polar Nonpolar Imino acid A- Amino Acids with Aliphatic R-Groups Glycine Gly -G 2.4 9.8 1-Simple Alanine Ala - A 2.4 9.9 pKa’s Valine Val - V 2.2 9.7 2- Leucine Leu -L 2.3 9.7 Branched AA”s Isoleucine Ile - I 2.3 9.8 26 Amino Acids with Polar R-Groups 3- Non-Aromatic Amino Acids with Hydroxyl R-Groups Serine Ser - S 2.2 9.2 ~13 Threonine Thr -T 2.1 9.1 ~13 4- Amino Acids with Sulfur-Containing R-Groups Cysteine Cys -C 1.9 10.8 8.3 Methionine Met-M 2.1 9.3 27 5-Acidic Amino Acids and Amide Conjugates Aspartic Asp - D 2.0 9.9 3.9 Acid Asparagine Asn - N 2.1 8.8 Glutamic Glu - E 2.1 9.5 4.1 Acid Glutamine Gln -Q 2.2 9.1 28 6- Basic Amino Acids Arginine Arg -R 1.8 9.0 12.5 Lysine Lys -K 2.2 9.2 10.8 Histidine His - H 1.8 9.2 6.0 29 B- Aromatic Amino Acids and Proline Phenylalanine Phe -F 2.2 9.2 Tyrosine Tyr -Y 2.2 9.1 10.1 Tryptophan Trp-W 2.4 9.4 Proline Pro - P 2.0 10.6 30 Amino Acids 3 October 2024 PROF Dr. Samy Abd Elfatah 31 -C-C-C-N-C-N Aromatic Amino Acids Map = N+ Trp W -C- Arg R N Basic -C- -OH -C-CONH2 -C-C-CONH2 Lys K Tyr Y Asn N Gln Q Amide -C-C-C-C-NH3 + -C- -C-C C His H Phe F Asp D Glu E Acidic N N+ -C-COOH -C-C-COOH Aliphatic Gly G Ala A A Val V Ile I Leu L -H C C C C -CH3 -C -C-C-C -C-C-C -C-OH Ser S Cys C -C-SH C C C HN C-COOH -C-C Non-polar OH Thr T Met M -C-C-S-C Pro P Imino Polar Hydroxy Sulfur ❖ Derived amino acids: ❑ Derived amino acids found in proteins: e.g. hydroxyproline & hydroxylysine. ❑ Derived amino acids not seen in proteins: e.g. ornithine;citrulline & homocysteine. ❑ Non –α-amino acids: e.g. - GABA is neurotransmitter in brain. - β-alanine is part of coenzyme A. - Taurine occurs in bile. 33 ❖ Derived amino acids: Hydroxyproline 5-hydroxylysine Citrulline Ornithine Taurine 34 Classification based on nutritional requirement: Essential and Non-essential 35 Dietary protein is the source of essential amino acids Dietary proteins provide the amino acids ….that humans cannot synthesize - the ….“essential” amino acids. The “non-essential” amino acids can be ….synthesized endogenously from ….intermediates of glycolysis or the TCA cycle. Mnemonic for essential amino acids: TRY THIS VIP MALL 36 Essential AAs: Non-essential AAs : Tryptophan Alanine Threonine Asparagine Histidine (for children only) Aspartate Valine Cysteine Isoleucine Glutamate Phenylalanine Glutamine Methionine Glycine Arginine (for children only) Proline Leucine Serine Lysine Tyrosine Mnemonic for essential amino acids: TRY THIS VIP MALL 37 Biological Value of Proteins ❖ Proteins which are digestible and contain all the essential amino acids are termed proteins of high biological value e.g. proteins of milk, meats and eggs. ❖ Proteins which are not digestible (e.g. collagen and elastin), or deficient in one or more of the essential amino acids (e.g. zein of maize and gliadine of wheat) are termed proteins of low biological value. ❖ Generally : Animal proteins are of high biological value. While plant proteins often lack one or more of the essential amino acids and have low biological value. 38 Animal protein = complete protein Vegetable protein = incomplete protein Amino Acid Deficiency in Selected Vegetables and Grains Protein supplementation or complementation It is possible to improve the quality of partially incomplete proteins by supplying the deficient amino acid. Eat 2 plant proteins together in the same meal that supplement each other. Examples: Wheat is low in lysine, and soybean is low in methionine. Mixing them together will create a complete protein mixture. Rice and beans make a completer protein combination. Classification based on metabolic fate of amino acids Ketoqenic Amino Acids: Leucine and lysine C-skeletons is converted to : Acetyl-CoA Acetoacetate Mixed Amino Acids: Phenylalanine, isoleucine, threonine, tyrosine and tryptophan Glucogenic Amino Acids: All the remaining 13 amino acids C-skeletons are converted to : Pyruvate α-Ketoglutarate Succinyl-CoA Fumarate Oxaloacetate (OAA) 42 4- Classification of Amino Acids by Polarity POLAR Acidic Neutral Basic Asp Asn Ser Arg Tyr Cys His Glu Gln Thr Lys POLAR Ala Ile Gly Phe Trp NON- Val Leu Met Pro Polar or non-polar, it is the basis of the amino acid properties. Properties of amino acids (Physical or Chemical) I- Physical properties of amino acids: Since multiple charged groups are present on amino acids, they are: 1) Readily solvated by water and hence soluble in polar solvents such as water. 2) Insoluble in non-polar (organic) solvents such as benzene, hexane or ether. 3) Precipitated from their aqueous solutions by alcohol. 4) Of high melting point (> 200°C) which reflects the high energy needed to disrupt the ionic forces that stabilize the crystal lattice. Properties of amino acids 5) Taste: Sweet: e.g. Glycine, alanine, valine, tryptophan, histidine and proline. Tasteless: e.g. leucine. Bitter: e.g. Isoleucine and arginine. Flavouring agent: e.g. Sodium glutamate. Artificial sweetener: e.g. Aspartame, an artificial sweetener contains aspartic acid and phenylalanine. 2- Isoelectric Point (pI): Amino acids are neutral at a pH, which is their isoelectric point (pI). Acidic environment Neutral environment Alkaline environment pK2 ~ 9 NH2 H+ NH2 H+ NH2 R-C-H R-C-H R-C-H COOH COO- COO- pK1 ~ 2 5.5 +1 0 -1 Isoelectric point Amino Acids Have Buffering Effect pH 12 ★ pK2 9 NH2 H+ 6 H-C-R Isoelectric point = pI COO- pK1 + pK2 3 ★ 2 pK1 0 [OH] → Amino Acid Chemistry 49 At isoelectric point the amino acid will carry no net charge; all the groups are ionized but the charges will cancel each other. Therefore, at isoelectric point there is no mobility in an electric field. Solubility and buffering capacity will be minimum at isoelectric point. To such a solution if we add HCl drop by drop, at a particular pH, 50% of the molecules are in cation form and 50% in Zwitterion form. This pH is PK1 (with regard to COOH). If more HCl is added, more molecules become cationic in nature and solubility increases. On the other hand, if we titrate the solution of form isoelectric point with NaOH, molecules acquire the anionic form, that pH is called PK2 (with respect to NH2). For monoamino monocaboxylic amino acid (neutral): PI = PK1 + PK2 e.g., PI of glycine = 2.4 + 9.8 = 6.1 2 2
