JX

Lesson 04: Biological Macromolecules

4.1 Introduction to Biological Macromolecules

Biological macromolecules are large, complex molecules synthesized by cells from small molecule subunits. They are organic molecules, with carbon serving as the framework.

Cell Composition

Cells are primarily composed of water. Macromolecules constitute approximately a quarter of the cell's mass.

  • Proteins: Make up roughly 15\% of a cell's mass.

  • Polysaccharides and Lipids: Each comprise about 2\% of a cell's mass.

  • Nucleic Acids (DNA and RNA): Comprise 7\% of a cell's mass, mostly RNA.

Carbon's Central Role

Carbon serves as the framework for most biological molecules, binding to other carbon atoms, or to hydrogen, oxygen, nitrogen, phosphorus, or sulfur atoms.

  • Hydrocarbons: Molecules composed entirely of hydrogen and carbon (e.g., butane, fatty acids).

    • Store energy in their many carbon-hydrogen bonds.

    • Nonpolar, due to similar electronegativity between hydrogen and carbon, thus interact poorly with water.

  • Polar Regions and Functional Groups: Molecules containing oxygen, nitrogen, sulfur, and phosphorus often have polar regions due to the electronegativity of these atoms. These regions are called functional groups and exhibit specific chemical properties.

    • Example: Alanine contains an amino group, a carboxyl group, and a methyl group.

Major Types and Functions of Biological Macromolecules

  1. Carbohydrates:

    • Energy storage molecules.

    • Provide structural support.

  2. Proteins:

    • Serve as enzymes.

    • Provide structural support.

    • Perform a wide range of other functions.

  3. Nucleic Acids:

    • DNA: Stores genetic information.

    • RNA: Involved in the expression of genetic information.

  4. Lipids:

    • Utilized in energy storage.

    • Provide the structure of cell membranes.

    • Act as signals for cell communication.

Macromolecule Subunits

  • Carbohydrates: Assembled from monosaccharide subunits.

  • Proteins: Assembled from amino acid subunits.

  • Nucleic Acids: Assembled from nucleotide subunits.

  • Lipids: Assembled from fatty acid subunits (relationship between subunit and macromolecule structure is more complex than for polymers).

  • Polymers: Carbohydrates, proteins, and nucleic acids are often termed polymers because they are formed from the end-to-end linkage of monomeric subunits.

4.2 Carbohydrates

Carbohydrates are assembled from monosaccharides (simple sugars).

Composition and General Properties

  • Contain carbon, hydrogen, and oxygen in a 1:2:1 ratio.

  • Often used as energy storage molecules due to many covalent bonds that release energy when broken.

  • Typically consist of three to six carbon atoms.

    • Five-carbon sugars play critical structural roles in nucleic acids.

    • Six-carbon sugars include glucose and fructose, both with the chemical formula C6H{12}O_6.

Structural Features of Monosaccharides

  • Isomers: Molecules with the same chemical formula but differing in structure or position of attached chemical groups.

    • Structural Isomers: Differ in the location of the carbonyl group (e.g., glucose has carbonyl at C1, fructose at C2).

      • Fructose forms a five-member ring, while glucose forms a six-member ring.

    • Stereoisomers: Have the same chemical groups but in opposite orientations (e.g., glucose and galactose differ at C4).

  • Glucose Example:

    • Linear six-carbon molecule that can form a six-member ring in solution.

    • Ring closure involves a covalent bond between the hydroxyl oxygen of C5 and C1.

    • Can result in two forms: alpha-glucose and beta-glucose, which differ in the position of the hydroxyl group bound to C1.

Disaccharides

  • Formed by the covalent linkage of two monosaccharides through a dehydration reaction (removal of a water molecule).

  • This reaction requires a cellular enzyme.

  • Functional roles: Can act as transport forms of sugars.

    • Sucrose: alpha-glucose linked with fructose (transport sugar in plants, table sugar).

    • Lactose: Glucose and galactose (transport role in mammals via milk).

Polysaccharides

  • Long polymers formed by the assembly of monosaccharides, often linked C1 of one subunit to C4 of the next.

  • Examples:

    • Starches (Amylose, Amylopectin):

      • Amylose: Unbranched, hundreds of subunits. Storage in plant cells.

      • Amylopectin: Branched. Storage in plant cells.

    • Glycogen: Similar storage function in animal cells.

    • Cellulose and Chitin: Serve structural roles in different types of organisms.

4.3 Nucleic Acids

Nucleic acids are polymers assembled from nucleotide subunits.

Nucleotide Composition

Each nucleotide contains three parts:

  1. Five-carbon pentose sugar (designated 1' to 5').

  2. Nitrogenous base (covalently attached to the 1' carbon of the sugar).

  3. At least one phosphate group (covalently attached to the 5'-carbon of the sugar).

Sugar Differences

  • Ribose (in RNA): Contains a hydroxyl group (-OH) on the 2' carbon.

  • 2'-deoxyribose (in DNA): Lacks an oxygen atom; contains only a hydrogen atom on the 2' carbon.

Nitrogenous Bases

Five types of bases, specified by single-letter abbreviations:

  • Purines (double-ring molecules):

    • Adenine (A)

    • Guanine (G)

  • Pyrimidines (single-ring molecules):

    • Cytosine (C)

    • Thymine (T) - found only in DNA

    • Uracil (U) - found only in RNA

  • Adenine, Guanine, and Cytosine are found in both DNA and RNA.

Polymer Assembly (Strand Formation)

  • Nucleotides are linked by phosphodiester bonds.

  • These bonds link the 3'-carbon of one subunit to the 5'-carbon of the next subunit.

  • Generates a directional polymer (strand) with a 5'-end and a 3'-end.

  • Genetic information in the sequence of bases is read starting from the 5'-end.

  • Sugar-phosphate backbone: Composed of the sugars and phosphate groups that link nucleotides together; bases project outward from this backbone.

DNA Structure

  • Contains two strands that interact via hydrogen bonds between complementary bases.

    • Adenine (A) bonds with Thymine (T).

    • Guanine (G) bonds with Cytosine (C).

  • The two strands twist into a double helical arrangement.

  • The two strands are anti-parallel: they run in opposite directions (e.g., 5'-end of one strand aligns with the 3'-end of the other).

  • The sequence of one strand can be deduced from the sequence of the other due to base pairing and anti-parallel arrangement.

Major Differences Between DNA and RNA

  1. Strandedness: DNA is double-stranded; RNA is single-stranded.

  2. Base Composition: DNA contains Thymine (T); RNA contains Uracil (U) instead of Thymine.

  3. Sugar Type: DNA contains 2'-deoxyribose; RNA contains ribose.

Adenosine Triphosphate (ATP)

  • Considered the energy currency of the cell.

  • Structure: Contains the base adenine linked to a ribose sugar, with three phosphate groups.

  • Chemical energy is stored in the linkage between the second and third phosphate groups, used to drive energetically unfavorable reactions in cells.

4.4 Proteins

Proteins are polymers of amino acids and perform a wide range of essential functions.

Amino Acid Structure

There are 20 types of amino acids, each characterized by:

  • A central carbon atom.

  • An amino group (-NH_2).

  • An acidic carboxyl group (-COOH).

  • A hydrogen atom.

  • A unique R-group (side chain): This group determines the specific chemical properties of each amino acid.

Amino Acid Classification (based on R-groups)

  • Nonpolar (10 amino acids).

  • Polar (10 amino acids):

    • Uncharged.

    • Negatively charged (acidic).

    • Positively charged (basic).

Specific Amino Acid Functions

  • Methionine: Generally the first amino acid in a protein's sequence.

  • Cysteine: Can form disulfide bonds with another cysteine, contributing to protein structure.

  • Proline: Creates kinks or turns in a protein structure.

Polymer Assembly (Polypeptide Formation)

  • Amino acids are linked by peptide bonds, which are covalent bonds formed through a dehydration reaction.

  • The carbon of the carboxyl group from one amino acid links to the nitrogen of the amino group of another.

  • This reaction is catalyzed by a large molecular machine called the ribosome.

  • Directionality: Polypeptides have an N-terminus (free amino group) and a C-terminus (free carboxyl group).

    • Assembly (synthesis) proceeds from the N-terminus to the C-terminus.

  • A polymer longer than ~10 amino acids is termed a polypeptide (average length ~300 amino acids).

  • Every protein has a unique amino acid sequence.

Levels of Protein Structure

The amino acid sequence (primary structure) ultimately determines a protein's structure and, in turn, its function.

  1. Primary Structure:

    • The unique, linear sequence of amino acids in a polypeptide chain.

    • Determined by covalent peptide bonds linking amino acids.

    • Changes in this sequence (e.g., due to mutations) can alter protein structure and function (e.g., Ras protein in cancer).

  2. Secondary Structure:

    • Involves interactions between amino acids relatively close in the sequence.

    • Generated by hydrogen bonds forming between atoms within the peptide backbone (not side chains).

    • Does not depend on amino acid side chains.

    • Two major types:

      • Beta sheet: A planar, flat sheet-like structure.

      • Alpha helix: A cylindrical structure.

  3. Tertiary Structure:

    • The overall three-dimensional shape of a single polypeptide chain.

    • Generated by interactions between amino acids that are far apart in the linear sequence, bringing together secondary structure elements connected by flexible loops.

    • Interactions primarily involve amino acid side chains:

      • Hydrogen bonds (between polar side chains).

      • Ionic interactions (between oppositely charged side chains).

      • Covalent disulfide bonds (between two cysteine residues).

      • Hydrophobic interactions (between nonpolar side chains, typically buried in the protein's interior away from water).

    • Often represents the functional form of the protein.

  4. Quaternary Structure:

    • Formed by the association of two or more polypeptide chains (called subunits) to form a functional protein.

    • Each polypeptide subunit typically folds into its tertiary structure before associating with others.

    • Interactions between subunits are the same types of bonds found in tertiary structure: hydrogen bonds, ionic interactions, disulfide bonds, and hydrophobic interactions.

Protein Stability and Denaturation

  • Denaturation: The process by which a protein loses its correct three-dimensional structure and becomes deactivated.

    • Caused by alterations in the environment, such as changes in pH, temperature, or ionic concentrations.

    • Results in the unfolding of the protein.

  • Renaturation: If the normal environmental conditions are restored, a denatured protein may refold into its original, active shape.