Proteins and Amino Acids Notes PDF

Module 2 PROTEINS & AMINO ACIDS BBIO109 Biochemistry John Dale Mateo, MAEd Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  LEARNING OBJECTIVES ✓ Classify proteins by their function ✓ Classify and name...

Module 2 PROTEINS & AMINO ACIDS BBIO109 Biochemistry John Dale Mateo, MAEd Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  LEARNING OBJECTIVES ✓ Classify proteins by their function ✓ Classify and name amino acids based on its structure and side chains at physiological pH ✓ Draw the structural formula for a peptide and give its name ✓ Describe the different protein structures ✓ Explain the physical and chemical factors that can denature proteins Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  WHAT IS A PROTEIN? Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  PROTEIN The word “protein” is derived from the Greek word proteios, meaning “first.” Proteins are large complex molecules made of amino acids joined by peptide bonds. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle There are many kinds of proteins that perform different functions Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle WHAT IS AN AMINO ACID? Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  AMINO ACID Proteins are composed of molecular building blocks called amino acids. There are only 20 different amino acids present in human proteins. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  AMINO ACID Every amino acid consists of a central carbon atom called the α-carbon bonded to two functional groups: an amino group (−𝑵𝑯𝟐 ) and a carboxylic acid group ( - COOH). The α-carbon is also bonded to a hydrogen atom and an R group. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  AMINO ACID It is the R group, which differs in each of the 20 amino acids, that provides unique characteristics to each type of amino acid. For example, alanine has a methyl, −𝐶𝐻3 , as its R group. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  IONIZATION OF AMINO ACID Although we have amino acids with uncharged amino (−𝑁𝐻2 ) and carboxylic acid (-COOH) groups, these groups are ionized for amino acids in most body fluids. At physiological pH, the −𝑵𝑯𝟐 group gains 𝑯 to give its + + ionized form −𝑵𝑯𝟑 and the –COOH group loses 𝑯 to + give its ionized form −𝑪𝑶𝑶 − Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  An ionized amino acid, which has both a positive and a negative charge, is a dipolar ion called zwitterion. The ionized regions have charge balance, which means that the ionized amino acid has an overall zero charge. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  AMINO ACID STEREOISOMERS All the α-amino acids except for glycine are chiral because the α-carbon is attached to four different atoms. Thus, amino acids can exist as D and L isomers. We can draw Fischer projections for α–amino by placing the carboxylate group at the top and the R group at the bottom. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  AMINO ACID STEREOISOMERS + In the L isomer, the −𝑁𝐻3 is on the left, and right in D isomer. In biological systems, the only amino acids incorporated into proteins are the L isomers. There are D amino acids found in nature, but not in proteins. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle CLASSIFICATION OF AMINO ACIDS Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Nonpolar Amino Acids Have hydrogen, alkyl, or aromatic R groups, w/c make them hydrophobic Polar Amino Acids Polar Neutral Have R groups that interact with Polar Acidic water, which makes them hydrophilic Polar Basic Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Polar Neutral AA Contain hydroxyl (-OH), thiol (-SH), or amide (−𝐶𝑂𝑁𝐻2 ), groups Polar Acidic AA R group contains a carboxylate group (−𝐶𝑂𝑂 ). − Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Polar Basic AA R group contains an amino group, which ionizes to give an ammonium ion Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Ionized Forms of Amino Acids A zwitterion with positive and negative charges and thus an overall neutral charge forms only at a certain pH called the isoelectric point (pI). However, an amino acid can exist: as a positive ion if a solution is more acidic (has a lower pH) than its pI as a negative ion if a solution is more basic (has a higher pH) than its pI. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Ionized Forms of Nonpolar and Polar Neutral Amino Acids The pI values for nonpolar and polar neutral amino acids are from pH 5.1 to 6.3. Alanine forms its zwitterion in a solution with a pH of 6.0, which is also its pI value. In the zwitterion form, alanine contains carboxylate anion (−𝑪𝑶𝑶 ) and an − + ammonium cation (−𝑵𝑯𝟑 ), which give an overall charge of zero. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Ionized Forms of Nonpolar and Polar Neutral Amino Acids In a solution with a pH lower than its pI (pH6.0), the −𝑵𝑯𝟑 loses 𝐻 to form an amino group (−𝑁𝐻2 ). + Because the −𝑪𝑶𝑶 remains ionized, alanine has an overall − negative charge (1-). Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Ionized Forms of Polar Acidic and Polar Basic Amino Acids The pI values of the polar acidic amino acids (aspartic acid, glutamic acid) are about pH 3. At pH values of 3, the carboxylic acid group in the R groups of their zwitterions is not ionized. However, at physiological pH values, which are greater than 3, the carboxylic acid in the R group loses 𝐻 to + form a negatively charged −𝑪𝑶𝑶 − Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Ionized Forms of Polar Acidic and Polar Basic Amino Acids The pI values of basic amino acids are typically higher than physiological pH value, ranging from pH 7.6 to 10.8. Thus, at physiological pH values, the amines in the R groups of the basic amino acids (lysine, arginine, and histidine) gain 𝐻 to + + form an overall positive charge −𝑵𝑯𝟑. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  LET US CHECK YOUR UNDERSTANDING Draw the condensed structural formula for the zwitterion for each of the following amino acids: a. Valine b. Serine Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  LET US CHECK YOUR UNDERSTANDING Which structure represents: A. Alanine at a pH above its pI? B. Alanine at a pH below its pI? Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  LET US CHECK YOUR UNDERSTANDING Consider the amino acid leucine with a pI of 6.0 A. At a pH of 3.0, how does leucine change? B. At a pH of 9.0, how does leucine change? Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  LET US CHECK YOUR UNDERSTANDING The pI of glycine is 6.0. Draw the condensed structural formulas for glycine at pH 6.0 and at pH 8.0. State the overall charge for each. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  LET US CHECK YOUR UNDERSTANDING The pI of glycine is 6.0. Draw the condensed structural formulas for glycine at pH 6.0 and at pH 8.0. State the overall charge for each. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  LET US CHECK YOUR UNDERSTANDING The pI of glycine is 6.0. Draw the condensed structural formulas for glycine at pH 6.0 and at pH 8.0. State the overall charge for each. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  EXERCISE Draw the condensed structural formula of serine at pH 3.0 and give the overall charge. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle FORMATION OF PEPTIDES Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  PEPTIDES A peptide bond is an amide bond that forms when the −𝑪𝑶𝑶 of− one amino acid reacts with the + −𝑵𝑯𝟑 of the next amino acid. The linking of two or more amino acids by peptide bonds forms a peptide. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Amidation reaction between the zwitterions of glycine and alanine + The AA glycine on the left with a free −𝑵𝑯𝟑 is called the N terminal AA. The AA alanine on the right with a free −𝑪𝑶𝑶 is called the C terminal AA. − Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Naming Peptides With the exception of the C terminal amino acid, the names of all the other amino acids in a peptide end with yl. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Naming Peptides For example, a tripeptide consisting of alanine at the N terminal, glycine, and serine at the C terminal is named as one word: alanylglycylserine. For convenience, the order of amino acids in the peptide is often written as the sequence of three-letter abbreviations. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  DRAWING PEPTIDES Draw the structure and give the name for the tripeptide Gly-Ser-Met Draw the structure for each amino acid in the STEP 1 peptide, starting with the N-terminus. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  DRAWING PEPTIDES Draw the structure and give the name for the tripeptide Gly-Ser-Met Remove the 0 atom from the carboxylate group of the N-terminal amino acid and two H atoms from the STEP 2 ammonium group in the adjacent amino acid. Repeat this process until the C-terminus is reached. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  DRAWING PEPTIDES Draw the structure and give the name for the tripeptide Gly-Ser-Met Use peptide bonds to connect the amino STEP 3 acids. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  EXERCISE Draw the peptide formed when the following amino acids bond: a. Val - Thr Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  PRACTICE Consider the dipeptide Val-Pro: a. What amino acid is the N terminal amino acid? b. What amino acid is the C terminal amino acid? c. Draw the formation of peptide. d. Give the name of the peptide. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  EXERCISE Consider the tripeptide below: a. What is the amino acid at the N terminal? What is the amino acid at the C terminal? b. Use the three-letter abbreviation of amino acids to give their order in the tripeptide. c. Give the name of the tripeptide. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  EXERCISE Given the amino acids Glycine – Alanine – Valine a. Draw the condensed structural formula of the tripeptide b. Give its name. c. Give its abbreviation. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle LEVELS OF PROTEIN STRUCTURE Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Primary Structure The primary structure of a protein is the particular sequence of amino acids held together by peptide bonds. For example, a hormone that stimulates the thyroid to release thyroxin is a tripeptide with the amino acid sequence Glu–His–Pro. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle The first protein to have its primary structure determined was insulin, which is a hormone that regulates the glucose level in the blood. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle In the primary structure of human insulin, there are two polypeptide chains. In chain A, there are 21 amino acids, and chain B has 30 amino acids. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  POLYPEPTIDES IN THE BODY Enkephalins and endorphins are natural painkillers produced in the body. They are polypeptides that bind to receptors in the brain to give relief from pain. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  POLYPEPTIDES IN THE BODY Two hormones produced by the pituitary gland are the nonapeptides (nine- amino-acid peptides) oxytocin and vasopressin. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Secondary Structure The secondary structure of a protein describes the type of structure that forms when amino acids form hydrogen bonds within a polypeptide or between polypeptides. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Secondary Structure The three most common types of secondary structure are the alpha helix, the beta- pleated sheet, and the triple helix.  Alpha Helix (α-helix) In an alpha helix (α-helix), hydrogen bonds form between the oxygen of the C=O groups and the hydrogen of N-H groups of the amide bonds in the next turn of the α-helix Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Beta-pleated Sheet (β-pleated sheet) In β-pleated sheet, hydrogen bonds form between the oxygen atoms in the carbonyl groups of one polypeptide chain and the hydrogen atoms in the N-H groups of the amide bonds in adjacent polypeptide chains. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Triple Helix Collagen, which is the most abundant protein in the body, makes up from 25% to 35% of all protein in vertebrates. The strong structure of collagen is a result of three α helical polypeptides woven together like a braid to form a triple helix. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Alzheimer’s Disease Alzheimer's disease is a form of dementia in which a person has increasing memory loss and inability to handle daily tasks. Alzheimer's patients have distinctly different brain tissue from people who do not have the disease. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle In the brain of a normal person, small beta-amyloid proteins, made up of 42 amino acids, exist in the alpha-helical form. In the brain of a person with Alzheimer's, the beta-amyloid proteins change shape from the normal alpha helices that are soluble, to sticky beta- pleated sheets, forming clusters of insoluble protein fragments called plaques. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Tertiary Structure The tertiary structure of a protein involves attractions and repulsions between the R groups of the amino acids in the polypeptide chain. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Tertiary Structure As interactions occur between different parts of the peptide chain, segments of the chain twist and bend until the protein acquires a specific three-dimensional shape. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle The tertiary structure of a protein is stabilized by interactions between the R groups of the amino acids in one region of the polypeptide chain and the R groups of amino acids in other regions of the protein Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Hydrophobic Interactions Are interactions between two nonpolar R groups. Within a protein, the amino acids with nonpolar R groups move away from the aqueous environment to form a hydrophobic center at the interior of the protein molecule. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Hydrophilic Interactions Are attractions between the external aqueous environment and the R groups of polar amino acids moving the polar amino acids toward the outer surface of globular proteins where they form hydrogen bonds with water. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Salt Bridges Are ionic bonds between ionized R groups of basic and acidic amino acids. For example, the ionized R group of arginine, which has a positive charge, can form a salt bridge (ionic bond) with the R group in aspartic acid, which has a negative charge. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Hydrogen Bonds Form between H of a polar R group and the O or N of another amino acid. For example, a hydrogen bond can form between the –OH groups of two serines or between the –OH of serine and the −𝑁𝐻2 in the R group of glutamine. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Disulfide Bonds (-S-S-) are covalent bonds that form between the –SH groups of cysteines in a polypeptide chain. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Exercise What type of attraction would you expect between the R groups of each of the following? A. Cysteine and cysteine B. Glutamic acid and lysine Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Globular Proteins A group of proteins known as globular proteins have compact, spherical shapes because sections of the polypeptide chain fold over on top of each other due to the various interactions between R groups. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Globular Proteins Myoglobin is a globular protein that stores oxygen in skeletal muscle. It contains 153 amino acids in a single polypeptide chain with about ¾ of the chain in the α-helix secondary structure. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Fibrous Proteins The fibrous proteins are proteins that consist of long, thin, fiber-like shapes. They are typically involved in the structure of cells and tissues. Two types of fibrous protein are the α- and β-keratins. α-keratins: hair, wool, skin, and nails β-keratins: feathers of birds and scales of reptiles Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Quaternary Structure When a biologically active protein consists of two or more polypeptide chains or subunits, the structural level is referred to as a quaternary structure. In the quaternary structure, the subunits are held together by the same interactions that stabilize tertiary structures. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Hemoglobin Hemoglobin, a globular protein that transports oxygen in blood, consists of four polypeptide chains or subunits: two α chains, and two β chains. In the adult hemoglobin molecule, all four subunits (𝜶𝟐 𝜷𝟐 ) must be combined for hemoglobin to properly function as an oxygen carrier. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Exercise Indicate which of the following are present in the primary, secondary, tertiary, and quaternary structures of proteins: a. Peptide bonds b. Hydrogen bonds between c. Hydrogen bonds within a single peptide d. Hydrophobic interactions e. Association of four polypeptide chains Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle DENATURATION OF PROTEINS Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Denaturation of Proteins Denaturation of a protein occurs when there is a change that disrupts the interactions between R groups that stabilize the secondary, tertiary, or quaternary structure. However, the covalent amide bonds of the primary structure are not affected. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle  Denaturation of Proteins The loss of secondary and tertiary structures occurs when conditions change, such as increasing the temperature or making the pH very acidic or basic. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Sickle-Cell Anemia Sickle-cell anemia is a disease caused by an abnormality in the shape of one of the subunits of the hemoglobin protein. In the β-chain, the sixth amino acid, glutamic acid, which is polar acidic, is replaced by valine, a nonpolar amino acid. Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle KAMSAHAMNIDA! Prepared by: John Dale Mateo, MAEd. Department of Natural Sciences. College of Arts and Sciences. University of St. La Salle