BBIO 109 Lecture Notes: Proteins and Acids (PDF)

BBIO 109 LECTURE NOTES MODULE 2: PROTEINS AND ACIDS Magbanua, Keilah What is a PROTEIN? characteristics to each type of amino acid. For example, alanine has a methyl, −𝐶𝐻3, as its R  The word “...

BBIO 109 LECTURE NOTES MODULE 2: PROTEINS AND ACIDS Magbanua, Keilah What is a PROTEIN? characteristics to each type of amino acid. For example, alanine has a methyl, −𝐶𝐻3, as its R  The word “protein” is derived from the Greek group. word proteios, meaning “first.”  Proteins are large complex molecules made of Ionization of Amino Acid amino acids joined by peptide bonds.  Although we have amino acids with uncharged  There are many kinds of proteins that perform amino (−𝑁𝐻2) and carboxylic acid (-COOH) different functions. 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−  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. What is an AMINO ACID?  Proteins are composed of molecular building blocks called amino acids.  There are only 20 different amino acids present in human proteins. 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  Every amino acid top and the R group at the bottom. consists of a central  In the L isomer, the −𝑁𝐻3+ is on the left, and carbon atom called right in D isomer. In biological systems, the the α-carbon only amino acids incorporated into proteins are bonded to two the L isomers. There are D amino acids found functional groups: in nature, but not in proteins. an amino group (−𝑵𝑯𝟐) and a CLASSIFICATION OF AMINO ACIDS carboxylic acid  Nonpolar Amino Acids group ( - COOH). The α-carbon is also bonded o Have hydrogen, alkyl, to a hydrogen atom and an R group. or aromatic R groups,  It is the R group, which differs in each of the 20 which make them amino acids, that provides unique hydrophobic BBIO 109 LECTURE NOTES MODULE 2: PROTEINS AND ACIDS Magbanua, Keilah  Polar Amino Acids POLAR NEUTRAL AMINO ACIDS o Have R groups that interact with water, which makes them hydrophilic o Polar neutral - Contain hydroxyl (-OH), thiol (- SH), or amide (−𝐶𝑂𝑁𝐻2), groups POLAR ACIDIC AMINO ACIDS o Polar Acidic - R group contains a carboxylate group (−𝐶𝑂𝑂−). o Polar Basic - R group contains an amino group, which ionizes to give an ammonium ion ESSENTIAL AMINO ACIDS POLAR BASIC AMINO ACIDS NONPOLAR AMINO ACIDS 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: BBIO 109 LECTURE NOTES MODULE 2: PROTEINS AND ACIDS Magbanua, Keilah o as a positive ion if a solution is more IONIZED FORMS OF POLAR ACIDIC AND acidic (has a lower pH) than its pI POLAR BASIC AMINO ACIDS o as a negative ion if a solution is more basic (has a higher pH) than its pI.  The pI values of the polar acidic amino acids (aspartic acid, glutamic acid) are about pH 3. At IONIZED FORMS OF NONPOLAR AND POLAR pH values of 3, the carboxylic acid group in the NEUTRAL AMINO ACIDS R groups of their zwitterions is not ionized. However, at physiological pH values, which are  The pI values for nonpolar and polar neutral greater than 3, the carboxylic acid in the R amino acids are from pH 5.1 to 6.3. Alanine group loses 𝐻+ to form a negatively charged forms its zwitterion in a solution with a pH of 6.0, which is also its pI value. In the zwitterion −𝑪𝑶𝑶− form, alanine contains carboxylate anion  The pI values of basic amino acids are typically higher than physiological pH value, ranging (−𝑪𝑶𝑶− ) and an ammonium cation (−𝑵𝑯𝟑+), from pH 7.6 to 10.8. Thus, at physiological pH which give an overall charge of zero. values, the amines in the R groups of the basic  In a solution with a pH lower than its pI amino acids (lysine, arginine, and histidine) gain (pH6.0), the −𝑵𝑯𝟑+ loses 𝐻+ to form an amino group (−𝑁𝐻2). Because the −𝑪𝑶𝑶− remains ionized, alanine has an overall negative charge (1-). BBIO 109 LECTURE NOTES MODULE 2: PROTEINS AND ACIDS Magbanua, Keilah FORMATION OF PEPTIDES 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.  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. 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. 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. BBIO 109 LECTURE NOTES MODULE 2: PROTEINS AND ACIDS Magbanua, Keilah DRAWING PEPTIDES Draw the structure and give the name for the tripeptide Gly-Ser-Met  STEP 1: Draw the structure for each amino acid in the peptide, starting with the N- terminus.  STEP 2: Remove the O atom from the carboxylate group of the N-terminal amino acid and two H atoms from the ammonium group in the adjacent amino acid. Repeat this process until the C-terminus is reached.  STEP 3: Use peptide bonds to connect the amino acids. BBIO 109 LECTURE NOTES MODULE 2: PROTEINS AND ACIDS Magbanua, Keilah o 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. LEVELS OF PROTEIN STRUCTURE  Primary Structure o The primary structure of a protein is the particular sequence of amino acids held together by peptide bonds. o For example, a hormone that stimulates the thyroid to release thyroxin is a - Two hormones produced by the tripeptide with the amino acid sequence pituitary gland are the Glu–His–Pro. nonapeptides (nine-amino-acid peptides) oxytocin and vasopressin. o The first protein to have its primary structure determined was insulin, which is a hormone that regulates the glucose level in the blood.  Secondary Structure o The secondary structure of a protein describes the type of structure that forms when amino acids o In the primary structure of human form hydrogen bonds within a insulin, there are two polypeptide polypeptide or between polypeptides. chains. In chain A, there are 21 o The three most common types of amino acids, and chain B has 30 secondary structure are the alpha helix, amino acids. the beta-pleated sheet, and the triple helix. o Alpha Helix (α-helix) - In an alpha helix (α-helix), hydrogen bonds form between the oxygen of the C=O groups and BBIO 109 LECTURE NOTES MODULE 2: PROTEINS AND ACIDS Magbanua, Keilah the hydrogen of N-H groups of inability to handle daily tasks. the amide bonds in the next turn Alzheimer's patients have of the α-helix distinctly different brain tissue from people who do not have the disease. - 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 o Beta-pleated Sheet (β-pleated sheet) beta-amyloid proteins change - In β-pleated sheet, hydrogen shape from the normal alpha bonds form between the oxygen helices that are soluble, to sticky atoms in the carbonyl groups of beta-pleated sheets, forming one polypeptide chain and the clusters of insoluble protein hydrogen atoms in the N-H fragments called plaques groups of the amide bonds in adjacent polypeptide chains. o Triple Helix  Tertiary Structure - Collagen, which is the most o The tertiary structure of a protein abundant protein in the body, involves attractions and repulsions makes up from 25% to 35% of all between the R groups of the amino protein in vertebrates. The strong acids in the polypeptide chain. structure of collagen is a result of three α helical polypeptides woven together like a braid to form a triple helix. o As interactions occur between different parts of the peptide chain, segments of o Alzheimer’s Disease the chain twist and bend until the protein acquires a specific three- dimensional shape. o 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 - Alzheimer's disease is a form of dementia in which a person has increasing memory loss and BBIO 109 LECTURE NOTES MODULE 2: PROTEINS AND ACIDS Magbanua, Keilah bridge (ionic bond) with the R group in aspartic acid, which has a negative charge. o HYDROGEN BONDS (Polar neutral and polar neutral – OH and – NH – or – NH2 ) - Form between H of a polar R group and the O or N of another o HYDROPHOBIC INTERACTIONS amino acid. For example, a (Nonpolar and nonpolar) hydrogen bond can form between - Are interactions between two the –OH groups of two serines or nonpolar R groups. Within a between the –OH of serine and the protein, the amino acids with nonpolar R groups move away −𝑁𝐻2 in the R group of from the aqueous environment to glutamine. form a hydrophobic center at the interior of the protein molecule. o DISULFIDE BONDS (- SH and – SH) o HYDROPHILIC INTERACTIONS - (-S-S-) are covalent bonds that (Polar neutral and water) form between the –SH groups of - Are attractions between the cysteines in a polypeptide chain. 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. o SALT BRIDGES (Polar basic – NH3+ and polar acidic – COO-) - 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 BBIO 109 LECTURE NOTES MODULE 2: PROTEINS AND ACIDS Magbanua, Keilah o Globular Proteins subunits are held together by the same - A group of interactions that stabilize tertiary proteins known structures as globular. proteins have compact, o Hemoglobin spherical shapes because sections - Hemoglobin, a globular protein of the polypeptide chain fold over that transports oxygen in blood, on top of each other due to the consists of four polypeptide chains various interactions between R or subunits: two α chains, and two groups. β chains. In the adult hemoglobin molecule, all four subunits (𝜶𝟐𝜷𝟐) - Myoglobin is a globular protein must be combined for hemoglobin that stores oxygen in skeletal to properly function as an oxygen muscle. It contains 153 amino carrier. acids in a single polypeptide chain with about ¾ of the chain in the α- helix secondary structure. Summary of Structural Levels in Proteins: o 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  Quaternary Structure o 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 BBIO 109 LECTURE NOTES MODULE 2: PROTEINS AND ACIDS Magbanua, Keilah 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.  The loss of secondary and tertiary structures occurs when conditions change, such as increasing the temperature or making the pH very acidic or basic. Examples of Protein Denaturation:  Sickle-Cell Anemia o 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.