Lecture 1 Amino Acid Peptides PDF

Lecture 1 Amino Acids & Peptides Applied Biochemistry (NUR 112) Second Semester 2023-2024 Instructor: Dr. Roba Bdeir Dr. Roba Bdeir 1 Amino Acids & Peptides: – What are amino acids, and what is their 3D structure? – What are the structures...

Lecture 1 Amino Acids & Peptides Applied Biochemistry (NUR 112) Second Semester 2023-2024 Instructor: Dr. Roba Bdeir Dr. Roba Bdeir 1 Amino Acids & Peptides: – What are amino acids, and what is their 3D structure? – What are the structures and properties of the individual amino acids? – Do amino acids have specific acid-base properties? – Which amino acids are essential and which are non-essential? – Some examples of non-standard amino acids? – What is the peptide bond? Dr. Roba Bdeir 2  Characteristics of Amino Acid Amino acids are basic units of protein They are soluble in water and insoluble in organic solvent More than 300 amino acids are found in nature Only 20 amino acids are standard and present in our protein because they are coded by our genes. Other non-standard amino acids are modified amino acids and called non-protein amino acids Lately two new ones were discovered: Selenocysteine and Pyrrolysine – They are rare mainly present in bacteria and archaea – They are not genetically coded (not found in our proteins) Dr. Roba Bdeir 3  Basic Amino Acid (aa) Structure All aa except proline has an asymmetric α-carbon attached to: – Carboxylic acid group (-COOH) – Primary amino group (-NH2) – hydrogen atom – R group, side chain aa differ only in R group and this difference gives a unique identity to each amino acid. In an aa, COOH has a pKa (~2); lower than that of carboxylic group (4-5) due to the nitrogen that acts as electron withdrawing group. Proline is NOT an aa but an imino acid. Dr. Roba Bdeir 4  Proline Proline is the only secondary (2°) amino acid or “imino” acid Amino acid Proline differs from the other 19 amino acids because: – It has secondary amino group. – The three carbon side chain is bounded to the amino group creating a cyclic molecule. – Its unique geometry contributes to formation of fibrous structure of collagen. – Not seen in α-helices Dr. Roba Bdeir 5  Stereochemistry of aa Stereochemistry is the three- dimensional shape of a molecule A.A. are optically active molecules and asymmetry of their mirror images is not superimposable → Such mirror images are said to be chiral. L- & D- forms If amino group is on the left side of -carbon → L FORM. If amino group is on the right side of -carbon → D FORM. Only L- form of amino acids are found in proteins in human body If D-form is present, it is converted into L-form by enzymes in liver D- amino acids are found in some antibiotics and in bacterial cell walls Dr. Roba Bdeir 6  Glycine All amino acids are chiral, four different groups bonded to α carbon, except in glycine. Glycine has two hydrogen atoms bonded to the α-carbon , the side chain (R group) of glycine is hydrogen. Glycine is not chiral is achiral. Dr. Roba Bdeir 7  Amino Acid Classifications These variations of the side chains R greatly influence the overall three dimensional structure, shape, conformation of a protein. They classified according to the side chain, R group: a. Amino acids with nonpolar side chains (hydrophobic). b. Amino acids with uncharged polar side chains. c. Amino acids with acidic side chains (negatively charged a.a). d. Amino acids with basic side chains (positively charged a.a). e. Amino acids with aromatic side chains. Dr. Roba Bdeir 8  A. nonpolar side chains: hydrophobic R is alkyl hydrophobic group which can NOT enter in H-bond formation. R-groups can be thought of as “oily” Achiral or “lipid like” → a property that promotes hydrophobic interactions. 9 aa are non polar: glycine, alanine, valine, leucine, Benzene ring isoleucine, phenylalanine, tryptophan, proline and methionine Highly hydrophobic = Indole ring Contains sulfur Imino acid Dr. Roba Bdeir 9  B. Uncharged polar side chains These a.a. have zero net charge at neutral pH Serine, threonine, tyrosine each contain a polar hydroxyl groups can participate in H-bonding. R-groups of asparagine and glutamine, containing an amide group each, can also participate in H-bonding. Side chains of cysteine and Amide group Amide group Disulfide bridge tyrosine can lose protons at C-S-S-C alkaline pH. Dr. Roba Bdeir 10  Cysteine: disulfide bond formation The cysteine contains a sulfhydryl (thiol) group (-SH), which is an important component of the active site at many enzymes. In proteins –SH groups of two cysteines can become oxidized to form a covalent crosslink called a disulfide bridge (-S-S-) The two –SH become oxidized to form a cysteine residue, i.e formation of disulfide bond by the oxidation of two cysteine residues producing one cystine residue. Dr. Roba Bdeir 11  Formation of cystine thiol group (—SH) Dr. Roba Bdeir 12  Location of Polar & Nonpolar aa in Proteins Proteins found in aqueous solutions: – Non-polar amino acids tend to cluster together in the interior of the protein – Nonpolar aa share only in hydrophobic interaction (No hydrogen or ionic bonds) – Polar uncharged aa are present outside of the soluble proteins and on surface of membrane associated proteins. The hydrophobic interaction is important in stabilizing protein structure. Alanine, valine, leucine and isoleucine play an important role in establishing and maintaining the 3D structures of proteins Cysteine has sulfhydryl group that can be oxidized to form a dimer, disulfide bridges called Cystine (C-S-S-C) Dr. Roba Bdeir 13 Proteins with polar and nonpolar aa Dr. Roba Bdeir 14  C. Acidic side chains At physiological pH, they will carry negative charge. Aspartic acid, Glutamic acid with carboxyl groups in their side chains are proton donors R-groups fully ionized, containing a negatively charged carboxylate group to COO- Aspargine and Glutamine: They are amide forms of aspartate & glutamate with the side chain COOH groups amidated. They are classified as neutral amino acids. Dr. Roba Bdeir 15  D. Basic side chains Contain 2 or more NH2 groups that act as base (bind H+) and are proton acceptor At physiologic pH, they will be fully ionized and positively charged Include Histidine, Lysine and Arginine Dr. Roba Bdeir 16  Amino Acids Their names Their structure NOTE: You need to know this table Their three letter code Uncharged polar Hydrophilic Hydrophobic Dr. Roba Bdeir 17 Hydrophobicity & its complexity Dr. Roba Bdeir 18  Amino Acid Chemistry In an A.A., i. Average pKa of an α–carboxyl group is 2.19 ii. Average pKa for an α–NH3+ group is 9.47 7/14/2024 Dr. Roba Bdeir 19  Zwitterion At physiological PH (7.4), -COOH gp is dissociated forming a negatively charged carboxylate ion (COO-) and amino gp is protonated forming positively charged ion (NH3+) = Zwitter ion In basic environment: aa dissociate proton to form carboxyl anion –COO-. Basic surround defends –NH2 against dissociation. In acidic environment: aa accept proton to form amonium cation –NH3+. Acidic environment defends –COOH against dissociation. 7/14/2024 Dr. Roba Bdeir 20  Isoelectric Point (pI) Zwitterionic structure is neutral and it is the pH at which a molecule carries no net electrical charge Each A.A. has ONE pI 7/14/2024 Dr. Roba Bdeir 21  Acidic & Basic Properties of AA Amino Acids can act as buffers. The quantitative relationship is described by Henderson-Hasselbalch equation: 7/14/2024 Dr. Roba Bdeir 22  Titration of AA When an amino acid is titrated, its titration curve represents the reaction of each functional group with a hydrogen ion – Titration curve of: Alanine is that of a diprotic acid Histidine is that of a triprotic acid Remember: When pH < pKa, the weak acid predominates H+ on, substance protonated When pH > pKa, the conjugate base predominates H+ off, substance deprotonated 7/14/2024 Dr. Roba Bdeir 23  Histidine An important amino acid in the function of many proteins and enzymes in terms of its pKa is histidine. With a pKa value near 6, the imidazole group can be uncharged or positively charged near neutral pH. Dr. Roba Bdeir 24  Aspartate (similar to glutamate) Net charges: +1 0 -1 -2 9 3 4 2 Dr. Roba Bdeir 25  Lysine (similar to arginine) Total +2 +1 0 -1 charges: pH < 2 9> pH > 3 pH > 10 pH > 11 Dr. Roba Bdeir 26  pKa Values of A.A. In free amino acids, α-carboxyl and α-amino groups are titratable groups. A.A. which the R group gets ionized: 1. Aspartic acid 2. Glutamic acid 3. Histidine 4. Cysteine 5. Tyrosine 6. Lysine 7. Arginine 7/14/2024 Dr. Roba Bdeir 27  Nutritional classification of aa 1) Essential amino acids: Can’t be synthesized de novo in the body i.e. essential to be taken in diet. Their deficiency affects growth, health and protein synthesis. 2) Semi-essential amino acids: 3) Non essential amino acids: Formed in the body but not in sufficient amount for body The rest of amino acids that are requirements especially in children. formed in the body in amount enough for adults and children. Summary of essential and semi-essential amino acids: They are the remaining 10 Valine Isoleucine Lysine Leucine amino acids. Arginine* Histidine* Methionine Tryptophan Threonine Phenylalanine *= arginine and histidine are semi-essential Dr. Roba Bdeir 28  non-standard aa Not coded in DNA Created by modification of standard amino acids that incorporated into polypeptide such as: – Histamine synthesized from histidine – Tyrosine is metabolized to epinephrine (adrenaline) – Tyrosine is also the precursor of the thyroid hormones thyroxine Dr. Roba Bdeir 29  Peptide bond formation Each polypeptide chain starts on the left side by free amino group termed (N- terminus), and ends on the right side by free COOH group termed (C-terminus) In proteins, all of carboxyl and amino groups combined in peptide linkage (repeating sequence of N-C-C-N-C-C) and are not available for chemical reaction except for H-bond The side chain or R group is not part of the backbone or the peptide bond Dr. Roba Bdeir 30