Macromolecules and Polymers Lecture

Introduction to Biological Macromolecules

• Course Objectives: The lecture focuses on identifying, building, and breaking down the four major biological macromolecules: carbohydrates, lipids, proteins, and nucleic acids.
• Hierarchical Scale of Organization: Life starts at the level of atoms, progresses to small molecules (understanding polarity and bonds like polar covalent, ionic, and hydrophobic interactions), and moves to intermolecular connections that form macromolecules. These macromolecules make up cells, which can form single-celled or multicellular organisms.
• Cellular Composition:
  • Any biological tissue (e.g., strawberries, animal tissue, green onions) is primarily composed of macromolecules.
  • The human body is approximately $70\,\%$ water and $23\,\%$ macromolecules.
• Distribution of Macromolecules:
  • Proteins: The most ubiquitous macromolecule in all living cells (bacterial, plant, fungal, archaeal, and human).
  • Nucleic Acids: Consist of DNA (Deoxyribonucleic Acid) and RNA (Ribonucleic Acid).
  • Carbohydrates: Various forms of sugars and polymers.
  • Lipids: Crucial for cell structure and protection.
• Organic Nature: All macromolecules are built on carbon-hydrogen skeletons. The interaction between carbon and hydrogen is the defining characteristic of organic molecules.

Polymer Chemistry: Synthesis and Degradation

• Monomers vs. Polymers:
  • A monomer is a single subunit.
  • A polymer is a chain made of multiple monomers coming together.
• The Big Three: Proteins, carbohydrates, and nucleic acids are all assembled and disassembled using the same chemical mechanisms.
• Lipid Exception: Lipids are not considered polymers in the strict sense because their subunits are not covalently bound together in repeating chains like the others.
• Dehydration Reaction (Synthesis):
  • This process builds polymers from monomers.
  • It is often referred to as a synthesis reaction.
  • Mechanism: A hydrogen ($H$) from one monomer and a hydroxyl group ($OH$) from another are removed to form a bond.
  • Result: One water molecule ($H_2O$) is lost (released) for every bond formed. For example, joining four monomers to a fifth results in a longer chain plus water.
• Hydrolysis Reaction:
  • This process breaks large molecules into smaller monomers or polymers.
  • Etymology: "Lysis" means to break, and "hydro" refers to water ("breaking with water").
  • Mechanism: Water is added to the reaction, providing the hydroxyl and hydrogen ends required to separate the bonded units.

Proteins: Structure and Nutrition

• Ubiquity: Proteins account for $50\,\%$ of the dry weight of most cells.
• Monomer: Amino acids are the building blocks of proteins.
• Chemical Structure of an Amino Acid:
  • Amino Group: Nitrogen-containing portion.
  • Carboxyl Group: The acid portion.
  • Alpha Carbon: The central carbon atom.
  • Side Group (R-group): A variable group that determines the chemical properties of the amino acid.
• R-Group Variability: There are 20 different amino acids categorized by their side chains:
  • Small vs. Large: Glycine has a tiny side chain (a single hydrogen atom), while Tryptophan has a massive aromatic ring structure.
  • Chemical Nature: Side chains can be hydrophobic (water-fearing) or hydrophilic (water-loving). Hydrophilic groups can be polar or electrically charged (positive or negative).
• Nutritional Categorization:
  • Complete Proteins: Foods that contain all essential amino acids (those the human body cannot synthesize and must ingest). Examples include milk, tofu, chicken, and beef.
  • Incomplete Proteins: Foods missing certain essential amino acids (e.g., almonds are high in protein but missing several essentials).
  • Complementary Proteins: Combining incomplete sources to create a complete profile. For example, White Rice lacks Lysine, and Lentils lack several others, but eating them together (Lentils and Rice) provides a complete protein profile.

The Four Degrees of Protein Folding

• Primary Structure: The linear sequence of amino acids joined by covalent peptide linkages. It resembles "beads on a string."
• Secondary Structure: The initial folding of the chain due to hydrogen bonding, creating alpha helixes (helical coils) and beta pleated sheets.
• Tertiary Structure: Continued complex folding of a single chain into a 3D shape, stabilized by covalent, ionic, and disulfide bonds.
• Quaternary Structure: The interaction and arrangement of multiple tertiary subunits (multi-chain structures). Most proteins in the human body exist in this state.
• Denaturation: Proteins are sensitive to their environment. Changes in temperature, $pH$, or salinity can cause them to "denature," or lose their shape and function. Straightening hair with heat is a practical example of temporarily altering protein shape.

Protein Function and Disease

• Functional Roles: Enzymes (catalysts), structural support (hair, horns), storage, and transport.
• Enzymes:
  • Names usually end in "-ase" (e.g., Lactase).
  • Substrate: The molecule the enzyme acts upon (e.g., Lactose ends in "-ose").
  • Active Site: The specific area where the substrate fits like a "lock and key."
  • Lactose Intolerance: Can be caused by an enzymatic malfunction where the active site changes shape, preventing the breakdown of lactose into glucose and galactose.
• Sickle Cell Anemia:
  • Caused by a single amino acid substitution (a mutation replacing one amino acid with Valine at position 6 in the hemoglobin chain).
  • This small change alters the entire morphology of the red blood cell, causing it to sickle and lose its affinity for oxygen and carbon dioxide.
• Prion Diseases:
  • Prions are misfolded, disease-causing proteins (not cells).
  • Mechanism: An unhealthy prion interacts with a healthy protein, causing it to misfold. This triggers a chain reaction (e.g., Mad Cow Disease).
• Molecular Mimicry: In research (e.g., the study of the bacterial virulence factor BTP1), bacteria may use amino acid sequences that mimic human proteins to suppress the immune response.

Carbohydrates: Sugars and Polymers

• Composition: Formations of carbon, hydrogen, and oxygen.
• Functions: Energy storage, energy transport, and structural carbon skeletons.
• Structural Varieties:
  • Cellulose: A linear polysaccharide found in plant cell walls (trees).
  • Starch: A branched polysaccharide found in plants (potatoes).
  • Glycogen: A highly branched polysaccharide used by humans for energy storage.
  • Chitin: Found in the shells of lobsters.
• Monomer and Polymer Terms:
  • Monosaccharide: Single sugar monomer (e.g., Glucose, Fructose, Ribose, Deoxyribose).
  • Disaccharide: Two monomers (e.g., Maltose, Sucrose).
  • Oligosaccharide: Multiple monomers.
  • Polysaccharide: Thousands of monomers.
• High Fructose Corn Syrup: Created by converting corn starch into glucose, then into fructose. The average American consumes roughly $45\,\text{kg}$ ($100\,\text{lbs}$) of sugar per year.

Lipids: Amphipathic Structures

• Amphipathic Nature: Lipids possess both a hydrophilic (water-loving) head and a hydrophobic (water-fearing) tail.
• Triglycerides: Consist of a glycerol head and three fatty acid tails.
• Saturation types:
  • Saturated Fats: Linear tails, no double bonds, "saturated" with hydrogen (e.g., butter). Generally considered less healthy.
  • Unsaturated Fats: Tails have double bonds that cause "kinks," missing hydrogens (e.g., oils). Generally considered healthy.
• Hydrogenated Oils: Unsaturated fats forced to accept hydrogens to increase shelf life and flavor (trans fats).
• Phospholipids: Form the basis of cell membranes. In water, they naturally form micelles, where heads face the water and tails crowd together inside.
• Other Lipids: Includes steroids (e.g., cholesterol), waxes (which repel water on leaves), and lipids for nerve protection.

Nucleic Acids and the Central Dogma

• General Structure: DNA and RNA are polymers made of nucleotide monomers.
• Nucleotide Components:
  1. A phosphate group.
  2. A pentose (5-carbon) sugar (Ribose in RNA, Deoxyribose in DNA).
  3. A nitrogenous base.
• Nitrogenous Bases:
  • DNA: Adenine ($A$), Thymine ($T$), Guanine ($G$), and Cytosine ($C$).
  • RNA: Adenine ($A$), Uracil ($U$), Guanine ($G$), and Cytosine ($C$).
• Base Pairing Rules:
  • In DNA, $A$ always pairs with $T$, and $C$ always pairs with $G$. They are held together by weak hydrogen bonds for easy "unzipping" to read the code.
  • Mathematical Relationship: If a sample has $28\,\%$ Adenine, it must have $28\,\%$ Thymine ($56\,\%$ total). The remaining $44\,\%$ is split equally between Guanine ($22\,\%$) and Cytosine ($22\,\%$).
• The Central Dogma: Describes the flow of genetic information.
  • DNA Replication: Making more DNA during cell division.
  • Transcription: Moving from $DNA \rightarrow RNA$.
  • Translation: Moving from $RNA \rightarrow \text{Protein}$ (translating the language of nucleotides into amino acids).
• Heredity: DNA is the "blueprint" for all living things, coordinating gene expression in every cell.

Summary Table of Macromolecules