Chapter 3: The Macromolecules of the Cell – Study Notes

The Macromolecules of the Cell

Introduction

Cells are composed of a variety of macromolecules that are essential for structure, function, and information storage. These macromolecules are typically polymers, synthesized by condensation reactions that link activated monomers through the removal of water. Most biological macromolecules are derived from about 30 common small molecules.

• Macromolecules include proteins, nucleic acids, polysaccharides, and lipids.

• Polymers are formed by condensation reactions (dehydration synthesis).

Proteins

Overview and Functions

Proteins are vital macromolecules found throughout all living cells, performing a wide range of functions.

• Enzymes: Catalyze biochemical reactions.

• Structural proteins: Provide support and shape (e.g., collagen, keratin).

• Motility proteins: Involved in movement (e.g., actin, myosin).

• Regulatory proteins: Control and coordinate cell functions.

• Transport proteins: Move substances across membranes.

• Signaling proteins: Facilitate communication between cells.

• Receptor proteins: Enable cells to respond to external stimuli.

• Defensive proteins: Protect against disease (e.g., antibodies).

• Storage proteins: Store amino acids for later use.

The Monomers: Amino Acids

• Proteins are polymers of amino acids (20 standard types used in protein synthesis).

• Each amino acid has a central (α) carbon, an amino group, a carboxyl group, a hydrogen atom, and a unique R group (side chain).

• All amino acids except glycine have an asymmetric α-carbon, giving rise to stereoisomers (L- and D-forms; only L-amino acids are found in proteins).

• The properties of amino acids depend on the nature of their R groups.

Classes of R Groups

• Nonpolar, hydrophobic R groups: 9 amino acids.

• Hydrophilic R groups: 11 amino acids (polar or charged at cellular pH).

• Acidic amino acids: Negatively charged.

• Basic amino acids: Positively charged.

• Polar amino acids: Often found on protein surfaces.

Polypeptides and Proteins

• Amino acids are linked by peptide bonds (covalent C–N bonds) formed via dehydration reactions.

• Polypeptides have directionality: N-terminus (amino end) and C-terminus (carboxyl end).

• The immediate product of amino acid polymerization is a polypeptide; it becomes a functional protein only after folding into a stable, biologically active shape.

Monomeric and Multimeric Proteins

• Monomeric proteins: Single polypeptide chain.

• Multimeric proteins: Two or more polypeptide chains (dimers, trimers, tetramers, etc.).

• Example: Hemoglobin is a tetramer (2 α and 2 β subunits).

Bonds and Interactions in Protein Folding and Stability

• Both covalent and noncovalent interactions are essential for protein conformation and stability.

• Interactions involve carboxyl, amino, and R groups (amino acid residues).

Disulfide Bonds

• Disulfide bonds: Covalent bonds between sulfur atoms of two cysteine residues (oxidation reaction).

• Provide significant stability to protein structure.

• Intramolecular (within same polypeptide) and intermolecular (between different polypeptides) types.

Noncovalent Bonds and Interactions

• Hydrogen bonds: Between R groups or backbone atoms; donors have H covalently linked to electronegative atoms, acceptors have electronegative atoms attracting H.

• Ionic bonds: Between oppositely charged R groups; sensitive to pH changes.

• Van der Waals interactions: Weak attractions between transient dipoles in nonpolar molecules.

• Hydrophobic interactions: Exclusion of hydrophobic side chains from water, driving protein folding.

Chaperone Interactions

• Molecular chaperones: Proteins that assist in the proper folding of other proteins, either during synthesis or refolding.

• They shield parts of the protein to prevent inappropriate interactions.

Levels of Protein Structure

• Primary structure: Amino acid sequence (covalent peptide bonds).

• Secondary structure: Local folding (α-helix, β-sheet) stabilized by hydrogen bonds.

• Tertiary structure: Three-dimensional folding due to interactions among R groups (hydrophobic, ionic, hydrogen bonds, disulfide bridges).

• Quaternary structure: Association of multiple polypeptides (same interactions as tertiary structure).

Level of Structure	Basis of Structure	Kinds of Bonds and Interactions Involved
Primary	Amino acid sequence	Covalent peptide bonds
Secondary	Folding into α-helix, β-sheet, or random coil	Hydrogen bonds between NH and CO groups in backbone
Tertiary	Three-dimensional folding of a single polypeptide	Disulfide bonds, hydrogen bonds, ionic bonds, van der Waals, hydrophobic interactions
Quaternary	Association of multiple polypeptides	Same as for tertiary structure

Native Conformation

• The most stable three-dimensional structure of a polypeptide is its native conformation.

• Proteins are classified as fibrous (elongated, structural) or globular (compact, functional).

Fibrous Proteins

• Extensive secondary structure, highly ordered and repetitive.

• Examples: Fibroin (silk), keratin (hair, wool), collagen (tendons, skin), elastin (ligaments, blood vessels).

Globular Proteins

• Most proteins are globular, folded into compact shapes with unique tertiary structures.

• Most enzymes are globular proteins.

Nucleic Acids

Overview

Nucleic acids are essential for storing, transmitting, and expressing genetic information. They are linear polymers of nucleotides.

• DNA: Deoxyribonucleic acid (genetic information storage).

• RNA: Ribonucleic acid (various roles in gene expression).

DNA and RNA Differences

• DNA contains deoxyribose; RNA contains ribose.

• DNA is the genetic repository; RNA is involved in expression and regulation.

The Monomers: Nucleotides

• Both DNA and RNA are composed of four types of nucleotides.

• Each nucleotide: five-carbon sugar, phosphate group, nitrogenous base (purine or pyrimidine).

• Purines: Adenine (A), Guanine (G); Pyrimidines: Cytosine (C), Thymine (T, in DNA), Uracil (U, in RNA).

The Polymers: DNA and RNA

• Nucleotides are joined by 3',5' phosphodiester bonds (phosphate group links two sugars).

• Polynucleotides have directionality: 5' phosphate end and 3' hydroxyl end.

• Sequences are written 5' to 3'.

Complementary Base Pairing

• A–T (DNA) or A–U (RNA): Two hydrogen bonds.

• G–C: Three hydrogen bonds.

• Base pairing is fundamental to nucleic acid structure and function.

Base Pairing in RNA

• RNA is usually single-stranded, but base pairing can occur within the molecule, forming secondary structures.

• Base pairing in RNA is less extensive than in DNA.

Polysaccharides

Overview

Polysaccharides are long-chain polymers of sugars and sugar derivatives, serving primarily structural and storage roles.

• Usually consist of repeating monosaccharide units or alternating patterns.

• Shorter chains (oligosaccharides) may be attached to cell surface proteins.

The Monomers: Monosaccharides

• Monosaccharides are simple sugars (e.g., glucose).

• Classified by carbon number: trioses (3C), tetroses (4C), pentoses (5C), hexoses (6C), heptoses (7C).

• Glucose (C6H12O6) is the most common monosaccharide.

Ring Forms of Glucose

• D-glucose forms two ring isomers: α (hydroxyl on C1 down) and β (hydroxyl on C1 up).

Disaccharides

• Formed by glycosidic bonds between two monosaccharides (e.g., maltose, lactose, sucrose).

• α-glycosidic and β-glycosidic bonds differ in the orientation of the linkage.

Storage and Structural Polysaccharides

• Starch (plants) and glycogen (animals, bacteria): Storage polysaccharides of α-D-glucose.

• Linked by α(1→4) glycosidic bonds; branching via α(1→6) bonds.

Lipids

Overview

Lipids are hydrophobic macromolecules, not formed by linear polymerization, but essential for energy storage, membrane structure, and signaling.

• Soluble in nonpolar solvents (e.g., chloroform, ether).

• Some are amphipathic (contain both polar and nonpolar regions).

Main Classes of Lipids

• Fatty acids

• Triacylglycerols (triglycerides)

• Phospholipids

• Glycolipids

• Steroids

• Terpenes

Fatty Acids

• Saturated: No double bonds, straight chains, pack tightly.

• Unsaturated: One or more double bonds, bent chains, less tightly packed.

• Trans fats: Unsaturated fats with trans double bonds, less bent, associated with health risks.

Triacylglycerols

• Glycerol + three fatty acids (linked by ester bonds).

• Main function: Energy storage.

• Saturated: Solid at room temperature (fats); Unsaturated: Liquid (oils).

Phospholipids

• Major membrane components due to amphipathic nature.

• Phosphoglycerides: Glycerol backbone, two fatty acids, phosphate group, and a small hydrophilic alcohol.

• Sphingolipids: Based on sphingosine, can form ceramides.

Glycolipids

• Lipids with carbohydrate groups (often derivatives of sphingosine or glycerol).

• Occur mainly on the outer plasma membrane.

Steroids

• Four-ringed hydrocarbon skeleton; hydrophobic.

• Cholesterol is the most common animal steroid.

Terpenes

• Formed from isoprene units; include vitamin A and carotenoids.