Amino Acids and Protein Chemistry PDF

Dr. Mahmoud Senousy Associate Professor of Biochemistry 1  CHAPTER OUTLINE Amino Acids and Proteins: Structure and functions Learning Objectives: After reading this chapter you should:  Be able to recognize the structur...

Dr. Mahmoud Senousy Associate Professor of Biochemistry 1  CHAPTER OUTLINE Amino Acids and Proteins: Structure and functions Learning Objectives: After reading this chapter you should:  Be able to recognize the structures of the 20 amino acids commonly found in proteins.  Know the properties of their side chains and how these properties affect protein structure.  Be able to recognize the structure of peptide bond.  Be able to describe the forces that determine how proteins fold.  Know the definitions of the four levels of protein structure.  Know what is meant by protein denaturation. 2 Proteins: The primary worker molecules in the body  Transport: hemoglobin in blood  Structural: collagen  Regulatory: enzymes and hormones  Storage: myoglobin in muscles  Contractile: myosin in muscles  Immune response: immunoglobulins (antibodies)  Receptors: sense stimuli e.g., in neurons 3 Proteins are polymers of amino acids linked by peptide bonds. Amino acids are the building blocks of proteins. Twenty standard (proteinogenic) amino acids are commonly found in mammalian proteins? Because they are encoded by genes in DNA. Proteins are synthesized in the RIBOSOME. RIBOSOME amino acids Proteins 4  Amino Acid Structure Common to all amino acids of proteins α Distinctive for each amino acid Between amino group and carboxylic group zwitterion α 5  Zwitterionic form of Amino Acids _ + pH 7.4 At physiologic pH, the carboxyl group is dissociated, forming the negatively charged carboxylate ion (–COO–), and the amino group is protonated (–NH3+). 6  Amino Acid Structure Carboxylic group - COO Amino group + H3 N aC H R group  Classification of Amino Acids  Amino acids can be classified according to: 1. Polarity of side chain (R): polar and non-polar. 2. Structure of side chain (R): aliphatic, aromatic, and imino acid. 3. Nutritional requirement: essential , conditionally essential, and non-essential. 4. Metabolic fate: ketogenic, glucogenic, and mixed amino acids. 8 1-Classification of amino acids based on the polarity of the side chains (R) Non-Polar Amino Acids (have an even distribution of electrons) Amino Polar Uncharged Acids Polar Amino Amino Acids Acids (have an uneven Acidic Amino distribution of Acids electrons) Basic Amino Acids 9 Non-Polar Amino Acids 10 11  Polar Amino Acids Uncharged 12  -C-C-C-N-C-N Aromatic = N+ -C- Amino Acids Map Trp W 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 a Non-polar OH Thr T Met M -C-C-S-C Pro P Imino Polar Hydroxy Sulfur 13 Abbreviations of Amino Acids 14 2-Classification based on the structure of R 2-Aromatic amino acids: Phenylalanine-Tyrosine-Tryptophan- Histidine 3-Imino acid: Proline 15  3-Classification based on nutritional requirements  Essential Amino Acids: amino acid that cannot be synthesized by our bodies, and thus must be supplied in our diet. Phenylalanine, Valine, Threonine, Tryptophan, Methionine, Leucine, Isoleucine, Lysine, and Histidine.  Conditionally Essential Amino Acids: their synthesis can be limited under special pathophysiological conditions (e.g., infants or in case of severe catabolic distress). Arginine, Cysteine, Glycine, Glutamine, Proline, and Tyrosine.  Non-Essential Amino Acids: can be synthesized in the body. Alanine, Aspartic Acid, Asparagine, Glutamic Acid, and Serine. 16  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, meat, and egg.  Proteins which are not digestible (e.g. collagen and elastin), or deficient in one or more of the essential amino acids (e.g. plant proteins) 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. 17  4-Classification based on the metabolic fate of amino acids  Ketoqenic Amino Acids: leucine and lysine Carbon skeletons are converted to ketone bodies.  Mixed Amino Acids: isoleucine, phenylalanine, tyrosine and tryptophan Carbon skeletons are converted to glucose and ketone bodies.  Glucogenic Amino Acids: All the remaining 14 amino acids Carbon skeletons are converted to glucose. 18  Optical Properties of Amino Acids The α-carbon of each amino acid is said to be chiral or asymmetric or optically active as it is attached to 4 different chemical groups EXCEPT glycine (the only amino acid that is optically inactive). Enantiomers : 2 stereoisomers that are mirror image to each other (D and L forms of amino acids) All of the amino acids in mammalian proteins exhibit L-configuration. D-amino acids are often found in polypetide antibiotics and bacterial cell walls. 19 Mirror Images of Amino Acid a Mirror image a Enantiomers  Derived (Non-Proteinogenic) Amino Acids  Derived amino acids found in proteins: After protein synthesis, the amino acid side chains of protein is modified e.g., 1- hydroxyproline and hydroxylysine in collagen 2- cystine is formed from oxidation of SH of two cysteine residues to form disulphide bond.  Derived amino acids not seen in proteins: come form metabolism and found as free amino acids in the cell e.g., 1- ornithine and citrulline (in urea cycle) 2- homocysteine (comes from methionine)  Non –α-amino acids: 1 – γ-aminobutyric acid (GABA): a neurotransmitter synthesized from decarboxylation of glutamate. 2-β-alanine is a part of coenzyme A. 3- Taurine present in bile acids or bile salts. 21  Derived (Non-Proteinogenic) Amino Acids 5-hydroxylysine Hydroxyproline Ornithine Citrulline Taurine 22  Selenocysteine: A Special Case  It is now considered the 21th proteinogenic amino acid, but it is a non-standard uncommon amino acid.  Selenocysteine is a special case. This rare amino acid residue is introduced during protein synthesis rather than created through a modification after protein synthesis.  Its structure contains selenium rather than the sulfur of cysteine.  Selenocysteine is a constituent of just a few proteins known as selenoproteins e.g., glutathione peroxidase enzyme. 23