Chapter 5: Macromolecules of Life - Comprehensive Notes
Macromolecules of Life
Introduction to Macromolecules
Macromolecules are also known as polymers.
They are composed of smaller individual units called monomers.
Dehydration Synthesis: This is a chemical reaction that joins monomers together to form a polymer. It involves the removal of a water molecule (H_2O) to create a new bond.
Example: HO - monomer1 + H - monomer2 \rightarrow HO - monomer1 - monomer2 + H_2O
Hydrolysis: This reaction breaks a polymer apart into its individual monomers. It involves the addition of a water molecule (H_2O), which breaks a bond.
Example: HO - polymer - H + H2O \rightarrow HO - monomer1 + H - monomer_2
Four Major Classes of Macromolecules
Proteins: Monomers are amino acids.
Carbohydrates: Monomers are sugars (monosaccharides).
Nucleic Acids: Monomers are nucleotides.
Lipids: Building blocks are fatty acids (though not true polymers in the same way as the others).
Molecular Logic of Life: "Small common monomers are ordered into unique macromolecules."
Carbohydrates / Polysaccharides
Monosaccharides (Simple Sugars)
General formula for common sugars is (C6H{12}O_6).
Can exist as linear structures.
Differences between sugars arise from:
Length of the carbon chain.
Presence of an aldose (aldehyde sugar) or ketose (ketone sugar) group.
Spatial arrangement around carbon atoms (leading to isomers).
Glucose Structure:
Exists in both linear and ring forms.
Chemical equilibrium strongly favors the formation of stable ring structures.
Carbons are numbered from 1 to 6.
To form the glucose ring, carbon 1 bonds to the oxygen attached to carbon 5.
Abbreviated ring structures often show unlabeled corners representing carbons, and a thicker edge indicating a 3D perspective.
Disaccharides
Formed when two monosaccharides are joined by dehydration synthesis.
The bond formed is a glycosidic bond.
Examples:
Maltose: Formed from two glucose molecules linked by a 1-4 glycosidic bond.
Sucrose: Formed from one glucose and one fructose molecule linked by a 1-2 glycosidic bond.
Polysaccharides (Complex Carbohydrates)
Used primarily for glucose storage; glucose monomers can be 'chopped off' by hydrolysis for cellular respiration.
Storage Polysaccharides:
Starch (in plants):
Amylose: An unbranched polymer of glucose monomers with 1,4 glycosidic linkages.
Amylopectin: A somewhat branched polymer with 1,4 linkages and 1,6 branches occurring approximately every 24 glucose molecules.
Glycogen (in animals):
The animal equivalent of starch, stored in muscle tissue and liver.
Much more extensively branched than amylopectin, with branches occurring approximately every 8-12 glucose molecules.
Structural Polysaccharides:
Cellulose (in plants):
Provides strength to plant cell walls.
Consists of unbranched straight chains of glucose.
Features beta-1,4 glycosidic linkages (unlike the alpha-1,4 linkages in starch).
Humans cannot digest cellulose because they lack enzymes to hydrolyze beta-1,4 linkages. It serves as a good source of fiber ("Insoluble Fiber" on food labels).
Hydrogen bonds between parallel cellulose molecules cause them to aggregate into strong microfibrils.
Chitin (in arthropods and fungi):
Forms the exoskeleton of insects and crustaceans and the cell walls of fungi.
Similar to cellulose but not made of pure glucose; it has a nitrogen-containing functional group attached to carbon 2 of the glucose monomer.
Lipids
Characteristics of Lipids
Primarily composed of hydrocarbons, which makes them hydrophobic (no affinity for water).
Fatty Acids: Long hydrocarbon chains with a carboxyl group at one end.
Triacylglycerol (fats): Consists of one glycerol molecule attached to three fatty acid molecules.
Function as a high energy storage molecule, providing approximately 2x the energy of glucose.
Types of Fats and Oils
Saturated Fatty Acids:
Contain no carbon-carbon double bonds, meaning their hydrocarbon chains are 'saturated' with hydrogen atoms.
Tend to be solid at room temperature (e.g., animal fats).
Unsaturated Fatty Acids:
Contain one or more carbon-carbon double bonds, creating kinks in their hydrocarbon chains.
Tend to be liquid at room temperature (e.g., plant oils).
Functions of Fats: Energy storage, cushioning of organs, insulation.
Phospholipids and Steroids
Phospholipids:
Composed of two fatty acids and one phosphate group attached to a glycerol molecule.
Exhibit an amphipathic nature:
Hydrophilic head: The phosphate group (and often an attached choline) is polar and attracted to water.
Hydrophobic tails: The fatty acid chains are nonpolar and repel water.
This dual nature allows phospholipids to form the phospholipid bilayer that constitutes all biological membranes.
Steroids:
Characterized by a carbon skeleton consisting of four fused rings.
Example: Cholesterol, a crucial component of animal cell membranes and a precursor for other steroids (like sex hormones).
Proteins
General Characteristics and Functions
Proteins account for approximately 50\% of the dry weight of a cell.
They perform a vast array of cellular functions:
Enzymatic proteins: Selective acceleration of chemical reactions (e.g., digestive enzymes).
Defensive proteins: Protection against disease (e.g., antibodies).
Storage proteins: Storage of amino acids (e.g., casein in milk, ovalbumin in egg white).
Transport proteins: Transport of substances (e.g., hemoglobin transports oxygen, membrane proteins transport molecules across cell membranes).
Hormonal proteins: Coordination of an organism's activities (e.g., insulin regulates blood sugar).
Receptor proteins: Response of a cell to chemical stimuli (e.g., nerve cell receptors).
Contractile and motor proteins: Movement (e.g., actin and myosin in muscles, proteins in cilia and flagella).
Structural proteins: Support (e.g., keratin in hair, collagen and elastin in connective tissues, silk fibers).
Monomers of proteins are amino acids; there are 20 different types.
Amino Acid Classification
All amino acids share a common core structure: a central alpha-carbon (\alpha-C) bonded to an amino group (NH_2), a carboxyl group (COOH), a hydrogen atom (H), and a variable side chain known as the R group.
The physical properties of the R group determine the characteristics of the amino acid and influence protein folding.
Amino acids are classified based on their R group properties:
Nonpolar (Hydrophobic) Amino Acids:
Glycine (Gly, G), Alanine (Ala, A), Valine (Val, V), Leucine (Leu, L), Isoleucine (Ile, I), Methionine (Met, M), Phenylalanine (Phe, F), Tryptophan (Trp, W), Proline (Pro, P).
Polar Uncharged (Hydrophilic) Amino Acids:
Serine (Ser, S), Threonine (Thr, T), Cysteine (Cys, C), Tyrosine (Tyr, Y), Asparagine (Asn, N), Glutamine (Gln, Q).
Electrically Charged (Hydrophilic) Amino Acids:
Acidic (negatively charged): Aspartic acid (Asp, D), Glutamic acid (Glu, E).
Basic (positively charged): Lysine (Lys, K), Arginine (Arg, R), Histidine (His, H).
Polypeptide Formation
Two amino acids are joined by a peptide bond formed through dehydration synthesis, resulting in a dipeptide.
A chain of many amino acids linked by peptide bonds is called a polypeptide.
Protein Conformation
"Structure determines function!!!!" The specific conformation (spatial arrangement of atoms) of a protein dictates its biological activity.
Proteins exhibit four levels of structural organization:
Primary Structure (1^o):
The unique linear sequence of amino acids in a polypeptide chain.
There is an infinite number of possible combinations with 20 amino acids.
Even a slight change in this sequence can fundamentally alter the protein's structure and function (e.g., sickle-cell disease).
The sequence of the first protein ever determined was insulin, using hydrolysis.
Secondary Structure (2^o):
Regular, localized folding patterns formed by hydrogen bonds between atoms of the polypeptide backbone (specifically, between the oxygen of a carboxyl group and the hydrogen of an amino group).
The R groups are not directly involved in forming the secondary structure.
Two main types:
Alpha-helix (\alpha-helix): A coiled structure stabilized by hydrogen bonds between the carbonyl oxygen of one amino acid and the amino hydrogen of an amino acid 4 residues away.
Beta-pleated sheet (\beta-pleated\ sheet): Individual polypeptide strands lie parallel or anti-parallel to each other, held together by hydrogen bonds between backbone atoms.
Tertiary Structure (3^o):
The overall three-dimensional shape of a single polypeptide chain, resulting from interactions between the R groups (side chains) of the amino acids.
These interactions include:
Covalent bonds: Disulfide bridges (S-S bonds) forming between the sulfhydryl groups of two cysteine residues.
Noncovalent interactions: Hydrogen bonds, ionic bonds, hydrophobic interactions, and van der Waals interactions.
Proteins can be filamentous (for support) or mostly globular.
Quaternary Structure (4^o):
Occurs when a protein is composed of two or more polypeptide chains (subunits) that aggregate to form a single functional macromolecule.
The term protein refers to the functional macromolecule, which may consist of one or several polypeptides.
Interactions between individual polypeptides (both covalent and noncovalent) hold the subunits together.
Example: Hemoglobin, which has four polypeptide subunits.
Consequences of Structural Alterations (Sickle-Cell Disease)
A single amino acid substitution in the primary structure of a protein can have profound effects.
Sickle-cell disease is caused by a single amino acid change in the beta subunit of hemoglobin.
Normal hemoglobin has Glutamic acid (Glu) at position 6.
Sickle-cell hemoglobin has Valine (Val) in place of Glu at position 6.
This substitution of a polar, charged amino acid (Glu) with a nonpolar, hydrophobic one (Val) leads to abnormal hydrophobic interactions between hemoglobin molecules.
The abnormal proteins aggregate into fibers, which deform red blood cells into a sickle shape, significantly reducing their oxygen-carrying capacity.
Protein Denaturation and Renaturation
Denatured protein: A protein that has lost its native three-dimensional structure and, consequently, its biological function (NONFUNCTIONAL).
Denaturation can be caused by changes in environmental conditions such as pH, salt concentration, or temperature.
Some denatured proteins can renature (refold) spontaneously when returned to a normal environment.
Other proteins require assistance from molecular chaperones (chaperonins). These proteins bind to newly synthesized or partially folded polypeptides, providing a protected environment to help them fold properly and prevent aggregation.
Nucleic Acids
Role and Central Dogma
DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are responsible for encoding and transmitting inheritable information.
DNA is the blueprint that programs a cell's activities, while proteins are the molecules that actually carry out most cellular functions (run the cell).
Central Dogma of Biology: The flow of genetic information in biological systems is typically from DNA
ightarrow RNA
ightarrow Protein.
Nucleotide Structure
The monomer of nucleic acids is a nucleotide, which consists of three components:
Nitrogenous Base:
Purines: Adenine (A) and Guanine (G) – double-ring structures.
Pyrimidines: Cytosine (C), Uracil (U, found in RNA), and Thymine (T, found in DNA) – single-ring structures.
Pentose Sugar (5-carbon sugar):
Ribose: Found in RNA, contains an -OH group on the 2'C (carbon).
Deoxyribose: Found in DNA, lacks an -OH group on the 2'C (hence 'deoxy').
Both have a hydroxyl (-OH) group on the 3'C, which is crucial for forming the phosphodiester linkage.
Phosphate Group: Attached to the 5'C of the sugar.
Polynucleotide: Nucleotides are joined together by phosphodiester linkages (covalent bonds) between the 3'C hydroxyl group of one nucleotide's sugar and the 5'C phosphate group of the next nucleotide.
DNA and the Genome
In 1953, James Watson and Francis Crick elucidated the 3-D structure of DNA as a double helix.
The DNA double helix consists of:
Two sugar-phosphate backbones forming the outside 'bars' of a ladder.
Nitrogenous bases projecting inward, forming the 'rungs' of the ladder.
The bases in opposite strands are paired by hydrogen bonds (A with T, and G with C).
Genome: The entire DNA content of an organism.
The genome is organized into individual functional segments called genes.
DNA Replication
The two strands of the DNA double helix are complementary (A always pairs with T, C always pairs with G) and antiparallel (one strand runs 5' to 3' and the other runs 3' to 5').
During DNA replication, each strand serves as a template for the synthesis of a new complementary strand (semiconservative replication). This mechanism also provides a crucial backup plan for correcting errors that may occur during replication.