Proteins

Proteins And Amino Acids

Page 1: Overview and Structural Representation

  • Learning context: Week 10
  • Picture sources:
    • https://natashaskitchen.com/pan-seared-steak/
    • https://lmu.pressbooks.pub/conceptsinbiology/chapter/protein-structure/
    • https://www.yummytummyaarthi.com/homemade-tofu-recipe-how-to-make-tofu/
    • https://aqueenathekitchen.com/simple-sweet-corn/
    • https://itsavegworldafterall.com/how-to-cook-chickpeas/
    • https://dairynutrition.ca/en/milk-quality/homogenization/why-milk-homogenized-and-what-are-its-effects

Page 2: Learning Objectives

  1. Draw the general structure for an α-amino acid, including the stereoisomer of standard amino acids.
  2. Classify α-amino acids as:
    • Nonpolar
    • Polar neutral
    • Polar acidic
    • Polar basic
  3. Describe essential amino acids, complete, and incomplete proteins.
  4. Describe the zwitterion structure adopted by amino acids at physiological pH.
  5. Describe the unique ability of the amino acid cysteine to form disulfide covalent bonds.
  6. Summarize the relationship between:
    • Peptide
    • Peptide bond
    • Amino acid residue
  7. Define the term primary protein structure.
  8. Describe the two most common types of protein secondary structure.
  9. Explain the role hydrogen bonding plays in the secondary structure of a protein.
  10. Describe the four types of attractive forces involved in tertiary protein structure.
  11. Distinguish tertiary protein structure from secondary protein structure in terms of how the peptide chains interact.
  12. Describe the difference between quaternary and tertiary protein structures.
  13. Differentiate between the terms: monomeric protein and polymeric protein.
  14. Describe the requirements for protein quaternary structure.
  15. Describe the conditions necessary for and the products produced when proteins are hydrolyzed.
  16. Describe the changes that occur structurally when a protein is denatured based on the denaturing agent.
  17. Describe the difference between fibrous or globular protein classifications.
  18. Classify proteins based on their functions in biochemical processes.
  19. Describe the five classes of plasma lipoproteins in terms of function and density characteristics.

Page 3: Amino Acids - Building Blocks of Proteins

  • Definition: Amino acids are the building blocks for proteins.
  • Protein: A protein is a naturally occurring, unbranched polymer in which the monomer units are amino acids.
  • α-Amino Acid: An organic compound that contains both an amino (—NH2) group and a carboxyl (—COOH) group attached to the α-carbon atom.
  • R Group (Side Chain): The R group differentiates different amino acids based on:
    • Size
    • Shape
    • Charge
    • Acidity
    • Functional groups present
    • Hydrogen-bonding ability
    • Chemical reactivity
  • Fischer Diagram: Illustrates the structure with stereochemistry, highlighting amino and carboxyl groups.

Page 4: Properties of the 20 Standard Amino Acids

  • Total Standard Amino Acids: 20 standard amino acids are normally found in proteins.
  • Polarity Classification of amino acids:
    • Nonpolar: 9
    • Polar neutral: 6
    • Polar acidic: 2
    • Polar basic: 3
  • Abbreviations: Each standard amino acid has both a three-letter and a one-letter abbreviation, which will be provided in the exam without labels.

Page 5: Non-Polar Amino Acids

  • Count: There are nine nonpolar amino acids:
    • Names: Glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan
    • Structural Characteristics:
    • Seven side chains are hydrocarbons.
    • Methionine has a thioether side chain.
    • Tryptophan possesses a nitrogen-containing heterocyclic ring structure.
  • Unique Characteristic: Proline has a propyl R group that forms a bond with the amino nitrogen atom.
  • Hydrophobic Nature: Nonpolar amino acids are generally located in the interior of proteins to avoid interaction with water.

Page 6: Polar, Neutral Amino Acids

  • Count: There are six polar neutral amino acids:
    • Names: Serine, threonine, tyrosine, cysteine, asparagine, glutamine
    • Structural Characteristics:
    • Three side chains are alcohols.
    • One is a thiol (cysteine).
    • Two contain amide groups.
  • Hydrophilic Nature: Polar neutral amino acids are more water-soluble due to their ability to hydrogen bond with water.

Page 7: Polar, Acidic Amino Acids

  • Count: There are two polar acidic amino acids:
    • Names: Glutamic acid, aspartic acid
    • Structural Characteristics:
    • Side chains contain a carboxylic acid group.
    • At physiological pH, the side chain is deprotonated.
  • Hydrophilic Nature: Polar acidic amino acids are more water-soluble due to their side chain's hydrogen bonding ability.

Page 8: Polar, Basic Amino Acids

  • Count: There are three polar basic amino acids:
    • Names: Histidine, arginine, lysine
    • Structural Characteristics:
    • Side chains contain an amino group.
    • The amino nitrogen is protonated and carries a positive charge at physiological pH.
  • Hydrophilic Nature: These amino acids exhibit enhanced water solubility due to potential hydrogen bonding with water.

Page 9: Essential Amino Acids

  • Definition: Not all amino acids are synthesized by the body.
  • Synthesis: Eleven amino acids can be synthesized in adequate amounts.
  • Essential Amino Acids: The nine essential amino acids must be obtained through dietary proteins due to inadequate synthesis:
    • Histidine
    • Phenylalanine
    • Isoleucine
    • Threonine
    • Leucine
    • Tryptophan
    • Lysine
    • Valine
    • Methionine
    • Note: Arginine is essential only for children, not adults.

Page 10: Dietary Protein Classification

  • Classification based on amino acid composition:
    1. Complete Dietary Protein: Contains adequate amounts of all essential amino acids.
    • Sources: Proteins from animals (milk, fish, eggs, meat) and soy.
    1. Incomplete Dietary Protein: Lacks adequate amounts of one or more essential amino acids relative to body needs.
    • Common in plant proteins; example: red beans and rice form a complete protein.
    • Gelatin is the only incomplete dietary protein from animals.

Page 11: Chirality of Amino Acids

  • Chirality: All amino acids are chiral except glycine, which has symmetric structures.
  • Characteristics of the α-carbon:
    • It serves as the chiral center, with four different groups attached.
  • Enantiomeric Forms: D and L forms exist; determined by the orientation of the amino group in Fischer projections.
    • The —NH2 group on the right indicates D and on the left indicates L.
    • The L-isomer is the form found in nature.

Page 12: Acid-Base Amino Acid Properties

  • Characteristics: Amino acids have both an acidic group (carboxyl) and a basic group (amino).
  • Reactions: They can be converted between neutral and charged states:
    • Amino group tends to gain a proton to form a positively charged ammonium ion.
    • Carboxyl group tends to lose its proton to form a negatively charged carboxylate ion.

Page 13: Zwitterions

  • Definition: Zwitterions are molecules with both a positive charge on one atom and a negative charge on another, resulting in a net charge of zero.
  • Existence: Amino acids exist as zwitterions in neutral solutions and solid states.
  • pH Effects:
    • In acidic solutions: carboxylate ion gets protonated.
    • In basic solutions: amino group gets deprotonated.
  • Physiological pH: The backbone of amino acids is zwitterionic at pH = 7.

Page 14: Zwitterion Equilibrium

  • Equilibrium: Different forms of the same amino acid exist in equilibrium, with dominant species depending on the pH.
  • Application: This equilibrium applies to nonpolar and polar neutral amino acids.
  • R Group: The R group does not undergo acid-base reactions.

Page 15: Cysteine and Disulfides

  • Characteristic: Cysteine is unique due to its ability to form disulfide bonds under physiologic conditions, contributing to protein structure and function.

Page 16: Drawing Amino Acids

  • Classification Table: The 20 standard amino acids are grouped according to the polarity of their side chains, listed with their structures, names, three-letter abbreviations, and one-letter abbreviations.

Page 17: Amide Bonds and Peptides

  • Definition: A peptide is an unbranched chain of amino acids connected through amide bonds.
  • Classification by Amino Acid Count:
    • Dipeptide: 2 amino acids
    • Tripeptide: 3 amino acids
    • Oligopeptide: 10-20 amino acid residues
    • Polypeptide: more than 20 amino acids
  • Amide Bonds: Involve a carbonyl and an amine, are stable and require significant conditions for hydrolysis (180 °C, 24 hours, and 6 M HCl).

Page 18: Peptide (Amide) Bonds

  • Formation: Peptide bonds are covalent bonds formed between the carboxyl group of one amino acid and the amino group of another.
  • Bonding Reaction: Similar to amide bond formation processes.

Page 19: Peptide Termini

  • Directionality: Peptides have directionality:
    • N-terminal end: Free amino group.
    • C-terminal end: Free carboxyl group.
  • Sequence Reading: Peptides are read from N-terminal to C-terminal, from left to right.
  • Amino Acid Residues: The part of the amino acid structure that remains in the peptide chain.

Page 20: Variable Regions in Peptides

  • Regions: Peptides have two regions:
    1. Backbone (repeating portion): Contains α-carbon and peptide bonds.
    2. Variable portion: R group side chains of amino acids, which form the unique sequence.

Page 21: Drawing a Peptide

  • Example: For peptide Ala-Tyr-Val:
    1. Draw line-angle structures of each amino acid.
    2. Link through amide bonds according to sequence.

Page 22: Classification of Standard Amino Acids

  • Table 20-1 repetition of amino acid structures with names and abbreviations for easy recall.

Page 23: Primary Protein Structure

  • Definition: Primary structure is the linear order of amino acids linked by peptide bonds.
  • N-to-C Terminal Order: Listed from N-terminal to C-terminal.
  • Species Variation: Primary structure can be similar in various species; e.g., cow and pig insulin compared to human insulin.

Page 24: Protein Secondary Structure

  • Definition: The spatial arrangement of the backbone in protein.
  • Types of Secondary Structures:
    1. Alpha helix (α-helix)
    2. Beta-pleated sheet (β-sheet)
  • Commonality: Proteins often contain both structures; rarely consist of only one.
  • Role of Hydrogen Bonds: Stabilize secondary structure.

Page 25: Hydrogen Bonding in Secondary Structure

  • Definition: Primary interaction maintaining secondary structure; involves interactions:
    • Carbonyl oxygen atom with hydrogen atom of another peptide linkage.
  • Running Antiparallel: The interacting backbones run in opposite directions.

Page 26: Secondary Structure: α-Helices

  • Definition: α-helix structure resembles a coiled spring maintained by hydrogen bonds.
  • Specific Features:
    1. Right-handed spiral twist.
    2. Hydrogen bonds are parallel to helix axis.
    3. Bonds occur between C═O and N—H groups four residues apart.
    4. One complete turn contains 3.6 amino acids.
    5. R groups extend outward from the helix.

Page 27: Secondary Structure: β-Sheets

  • Definition: β-pleated sheets are characterized by extended chain segments lying alongside each other.
  • Bonding: Hydrogen bonds between N—H and C═O groups of peptide backbone.
  • Formation Types: Can occur between separate chains or within a single chain folded back on itself.

Page 28: H-Bonds in β-Sheets

  • Key Features:
    1. Hydrogen bonds lie within the plane of the sheet.
    2. Folds occur at the alpha carbon.
    3. R groups alternate above/below the plane.
    4. Antiparallel interactions between chains.

Page 29: Unstructured Regions in Proteins

  • Definition: Segments that are neither α-helix nor β-sheet, yet provide functional structure.
  • Importance: Essential for protein function and flexible interactions.
  • Identical Segments: Proteins may contain multiple identical unstructured segments.

Page 30: Tertiary Protein Structure

  • Definition: The overall three-dimensional shape of a protein from amino acid side chain interactions within a single peptide chain.
  • Types of Interactions:
    1. Covalent disulfide bonds
    2. Salt bridges
    3. Hydrogen bonds
    4. Hydrophobic/hydrophilic interactions

Page 31: Tertiary Structure: Disulfide Bonds

  • Definition: Covalent bonds between two cysteine residues’ —SH groups.
  • Characteristics:
    • Strongest interaction involved in tertiary structure.
    • Can occur intramolecularly (within one chain) or intermolecularly (between different chains).

Page 32: Salt Bridges and Hydrogen Bonds

  • Salt Bridges: Electrostatic interactions between the -COO- of acidic side chains and the -NH3+ of basic.
  • Hydrogen Bonds: Occur between polar amino acid side chains; can be disrupted by changes in pH and temperature.

Page 33: Hydrophobic Interactions

  • Definition: Occur when two nonpolar amino acids are in proximity, directing nonpolar side chains inward while attempting to avoid water.
  • London Forces: Weak attractive forces between nonpolar side chains contributing cumulatively to the folding of proteins.

Page 34: Monomeric and Multimeric Proteins

  • Classification:
    • Monomeric Protein: Contains one peptide chain.
    • Multimeric Protein: Contains two or more peptide chains.
  • Subunits: Individual peptide chains, can be identical or different.
  • Common Combinations: Two subunits = dimer; four subunits = tetramer, generally even-numbered subunits.

Page 35: Quaternary Structure

  • Definition: The overall three-dimensional structure resulting from the organization of two or more peptide subunits in a multimeric protein.
  • Similar Interactions: Includes disulfide linkages, hydrogen bonds, salt bridges, and hydrophobic interactions.
  • Stability: Noncovalent interactions between subunits tend to be weaker and more easily disrupted compared to tertiary interactions.

Page 36: Quaternary Structure of Hemoglobin

  • Composition: Hemoglobin is a tetramer with two sets of identical subunits (two α subunits and two β subunits).
  • Interaction: Each subunit interacts with a heme unit, which is a prosthetic group essential for binding oxygen.

Page 37: Summary of Protein Structure

  • Summarized Definitions and Characteristics:
    • Primary Structure: Linear amino acid sequence.
    • Secondary Structure: Regular arrangements stabilized by hydrogen bonds (α-helix and β-sheet).
    • Tertiary Structure: 3D shape from side chain interactions (disulfide, salt bridges, hydrogen bonds, hydrophobic interactions).
    • Quaternary Structure: Multi-subunit organization and interaction.

Page 38: Protein Hydrolysis

  • Definition: Hydrolysis of peptide bonds in proteins, producing free amino acids.
  • Conditions: Strong acidic or basic solutions, heated or enzyme catalyzed.
  • Types:
    • Complete Hydrolysis: Breaks all peptide bonds, yielding only free amino acids.
    • Partial Hydrolysis: Some bonds are broken, yielding a mixture of free amino acids and peptides.
  • Effect: Results in the loss of primary structure.

Page 39: Complete Hydrolysis of a Tripeptide

  • Process: Hydrolysis of both peptide bonds in a tripeptide.
  • Protonation States: Resulting amino acids' protonation states depend on surrounding pH conditions:
    • Acidic: -COOH and -NH3+
    • Basic: -COO- and -NH2

Page 40: Protein Denaturation

  • Definition: Disorganization of a protein's three-dimensional shape, disrupting structural interactions.
  • Effect on Structure: Primary structure remains intact, but secondary and tertiary structures are lost.
  • Renaturation: The potential to refold into the original shape might exist post-denaturation, depending on the extent of denaturation.
  • Consequences: Loss of solubility and biochemical activity.

Page 41: Denaturing Agents

  • Common Agents and Their Modes of Action:
    • Heat: Disrupts hydrogen bonds and hydrophobic interactions (e.g., cooking).
    • Microwave Radiation: Causes violent molecular vibrations, disrupting bonds.
    • Detergents: Disrupt hydrophobic interactions, affecting proteins’ functionality.
    • Organic Solvents: Interfere with R-group interactions, can denature proteins quickly.
    • Strong Acids/Bases: Disrupt salt bridges, may lead to peptide bond hydrolysis.
  • Other Agents: Heavy metals can form toxic salts with thiol groups.

Page 42: Protein Shapes

  • Classification by Shape:
    • Fibrous Proteins: Organized long structures running in one direction (e.g., α-keratin).
    • Globular Proteins: Spherical or globular shapes (e.g., hemoglobin).
    • Membrane Proteins: Found associated with cellular membranes.

Page 43: Protein Classification Part 1

  • Protein Functions:
    1. Catalytic Proteins (Enzymes): Biochemical catalysts in metabolic reactions.
    2. Defense Proteins (Antibodies): Central to immune function against pathogens.
    3. Transport Proteins: Bind and transport molecules through the body (e.g., hemoglobin).

Page 44: Protein Classification Part 2

  • Continued classification based on functions:
    1. Messenger Proteins: Transmit signals to coordinate body processes (e.g., hormones).
    2. Contractile Proteins: Essential for movement (e.g., actin and myosin in muscles).
    3. Structural Proteins: Provide rigidity (e.g., collagen in cartilage).

Page 45: Protein Classification Part 3

  • Further classification:
    1. Transmembrane Proteins: Span cell membranes, controlling small molecules' movement.
    2. Storage Proteins: Bind/store small molecules (e.g., myoglobin for oxygen storage).
    3. Regulatory Proteins: Bind to enzymes and hormones, controlling their activity.

Page 46: Protein Classification Part 4

  • Completing the classification:
    1. Nutrient Proteins: Provide essential amino acids for growth (e.g., casein).
    2. Buffer Proteins: Maintain acid-base balance in fluids (e.g., hemoglobin's buffering).
    3. Fluid-Balance Proteins: Help maintain fluid balance using osmotic pressure.

Page 47: Blood Cholesterol

  • Form in Blood: Primarily exists as cholesterol esters due to the esterification with fatty acids.
  • Transport: Nonpolar cholesterol is carried by lipoproteins in aqueous blood.

Page 48: Plasma Lipoproteins

  • Definition: Conjugated proteins with lipids, crucial for lipid transport in the bloodstream.
  • Structure Characteristics:
    • Nonpolar lipid-core (triacylglycerols/cholesterol esters).
    • Polar shell formed of phospholipids, cholesterol, and proteins facing outwards toward the blood's aqueous environment.

Page 49: Types of Lipoproteins

  • Classification of Major Plasma Lipoproteins:
    1. Chylomicrons: Transport dietary triacylglycerols from intestines to tissues.
    2. Very-low-density lipoproteins (VLDLs): Transport triacylglycerols from the liver.
    3. Intermediate-density lipoproteins (IDL): Precursor of low-density lipoproteins (LDL).
    4. Low-density lipoproteins (LDLs): Transport cholesterol synthesized in the liver to cells.
    5. High-density lipoproteins (HDLs): Gather excess cholesterol and deliver it back to the liver for degradation.