Chapter 5: The Structure and Function of Large Biological Molecules
Concept 5.1: Macromolecules are polymers, built from monomers
Macromolecule definition: a large molecule composed of thousands of covalently connected atoms
Polymer definition: a long molecule consisting of many similar building blocks (monomers)
Four classes of large biological molecules in living organisms: carbohydrates, lipids, proteins, and nucleic acids
Monomers are the building blocks from which polymers are constructed
In cells, small organic molecules are joined to form larger macromolecules
Molecular structure and function are inseparable: structure determines function and vice versa
Synthesis and breakdown of polymers:
Condensation reaction (dehydration reaction): two monomers bond with loss of water
Enzymes: macromolecules that speed up dehydration reactions
Polymers can be disassembled to monomers by hydrolysis, the reverse reaction
The Synthesis and Breakdown of Polymers Animation (conceptual reference)
Diversity of polymers:
Each cell has thousands of different macromolecules
Macromolecules vary among cells, within species, and between species
A vast variety of polymers can be built from a small set of monomers
Concept 5.2: Carbohydrates serve as fuel and building material
Carbohydrates include sugars and the polymers of sugars
Monosaccharides: simple sugars, building blocks of carbohydrates
Polysaccharides: polymers of sugars; storage and structural roles
Monosaccharides as fuels and raw materials for building other molecules
Carbohydrate monomers and polymers are linked by glycosidic linkages
Monosaccharides are the harbor for energy storage and quick cellular fuel
Monosaccharides are classified by:
The location of the carbonyl group: aldose (aldehyde) or ketose (ketone)
The number of carbons in the carbon skeleton
Sugars: general facts
Monosaccharide formulas are usually multiples of
Glucose formula:
Examples of monosaccharides (common in biology):
Hexoses: glucose, galactose, fructose (glucose and galactose are aldoses; fructose is a ketose)
Pentoses: ribose, deoxyribose
Triose: glyceraldehyde
Monosaccharides in aqueous solution often form rings rather than linear structures
Functions of monosaccharides:
Major fuel for cells
Raw material for building other molecules
Disaccharides: formed when dehydration reaction joins two monosaccharides; glycosidic linkage
Examples of disaccharides and linkages:
Sucrose: glucose + fructose; linkage type: 1–2 glycosidic linkage
Maltose: glucose + glucose; linkage type: 1–4 glycosidic linkage
Polysaccharides (polymers of sugars): storage and structural roles
Storage polysaccharides:
Starch (plants): storage of glucose; granules in chloroplasts and other plastids
Glycogen (animals): storage of glucose in liver and muscle cells
Structural polysaccharides:
Cellulose (plants): polymer of glucose, but with beta (β) linkages; major component of plant cell walls
Chitin (arthropods and fungi): structural polysaccharide; exoskeletons in arthropods and fungal cell walls
Key structural distinction between starch and cellulose: α‑glucose vs β‑glucose linkages lead to different shapes
Polymers with α glucose tend to be helical; β glucose form straight chains capable of hydrogen bonding between parallel strands
This bonding yields microfibrils, which are strong building materials for plants
Figure references (conceptual):
Fig. 5-4: forms of glucose (linear and ring forms)
Fig. 5-7: starch vs cellulose linkages and ring conformations
Fig. 5-8: cellulose microfibrils
Digestive and ecological notes:
Enzymes that digest starch hydrolyze α-linkages but not β-linkages in cellulose
In humans, cellulose passes through digestive tract as insoluble fiber
Some microbes can digest cellulose; many herbivores rely on symbiotic microbes for cellulose digestion
Concept 5.3: Lipids are a diverse group of hydrophobic molecules and are not macromolecules
Lipids do not form polymers
Unifying feature: lipids have little or no affinity for water; hydrophobic due to nonpolar covalent bonds in hydrocarbon chains
Major lipid classes:
Fats (triacylglycerols or triglycerides)
Phospholipids
Steroids
Fats:
Constructed from glycerol and fatty acids
Glycerol: a three-carbon alcohol:
Fatty acid: carboxyl group attached to a long carbon skeleton; general formula
A fat consists of glycerol linked to three fatty acids via ester linkages (a dehydration/condensation process) forming a triacylglycerol
Synthesis of a fat (Fig. 5-11):
Dehydration reaction forms ester linkages between glycerol and fatty acids
Resulting fat molecule: triacylglycerol (triglyceride)
Fatty acids vary in length and in the number and positions of double bonds
Saturated fatty acids: maximum number of hydrogens; no double bonds
Unsaturated fatty acids: one or more double bonds (present as cis bonds in naturally occurring fats)
Hydrogenation can convert unsaturated fats to saturated fats and can create trans double bonds
Health implications:
Diet rich in saturated fats may contribute to cardiovascular disease via plaque formation
Hydrogenation produces trans fats, which may contribute more to cardiovascular disease
The major functions of fats:
Energy storage in animals
Adipose tissue provides organ cushioning and insulation.
Phospholipids: Glycerol + two hydrophobic fatty acids + hydrophilic phosphate head. Form cell membrane bilayers in water.
Steroids: Lipids with four fused carbon rings; Cholesterol is vital for animal membranes but high levels can be detrimental.
Lipids Summary: Not polymers, hydrophobic, crucial for structure, energy storage, membranes, and signaling.
Concept 5.4: Proteins have many structures, resulting in a wide range of functions
Proteins comprise over 50% of cell dry mass, performing diverse roles: enzymatic, structural, storage, transport, hormonal, receptor, movement, and defense.
Key Functions Examples: Digestive enzymes, collagen, hemoglobin, insulin, antibodies, actin/myosin.
Protein Structure Levels:
Primary: Unique sequence of amino acids.
Secondary: Coils (α-helix) and folds (β-pleated sheet) from hydrogen bonds along the backbone.
Tertiary: 3D shape stabilized by R-group interactions.
Quaternary: Multiple polypeptide chains associating.
Enzymes: Proteins that speed up chemical reactions, reusable 'workhorses'.
Amino Acids: 20 standard types; basic structure is amino group (), carboxyl group (), R group, and α-carbon. R groups determine properties.
Peptide Bonds: Covalent bonds linking amino acids via dehydration, forming the protein backbone.
Protein Folding: Amino acid sequence dictates 3D structure, which determines function.
Sickle-cell disease: A single amino acid change in hemoglobin alters its structure and oxygen function.
Denaturation: Loss of a protein's active structure due to environmental factors (pH, temp, salt), rendering it inactive. Some proteins can renature.
Chaperonins: Proteins that assist in proper folding of other proteins.
Structure Determination Methods: X-ray crystallography, NMR spectroscopy, Bioinformatics.
Concept 5.5: Nucleic acids store and transmit hereditary information
Genes: Units of inheritance, program polypeptide sequences.
Nucleic acids: Polynucleotides (DNA and RNA).
Roles:
DNA replicates itself, directs mRNA synthesis, and controls protein synthesis at ribosomes.
Central Dogma: DNA → RNA → protein.
Nucleic Acid Structure:
Polynucleotides: Nucleotides linked by phosphodiester bonds forming a sugar–phosphate backbone with nitrogenous bases.
Nucleotide: Nitrogenous base + pentose sugar + phosphate group.
Nucleoside: Nitrogenous base + sugar.
Nitrogenous Bases:
Purines: Adenine (A), Guanine (G) (two-ring).
Pyrimidines: Cytosine (C), Thymine (T) in DNA, Uracil (U) in RNA (single-ring).
Sugars: Deoxyribose (DNA) vs. Ribose (RNA).
DNA Double Helix: Two antiparallel polynucleotide strands. Bases pair via hydrogen bonds: A-T (2 bonds) and G-C (3 bonds).
DNA as a Chronicle: Sequence similarity reflects evolutionary relationships; used to assess kinship.
Gene Expression: DNA transcribed to mRNA (nucleus); mRNA translated to proteins (ribosomes).
Additional themes and cross-cutting ideas
Emergent properties: New properties arise at higher levels of biological organization.
Evolution: DNA sequence similarity indicates evolutionary relatedness among species.
Recall Check: Understand major macromolecules, linkages (glycosidic), fat types (saturated/unsaturated, cis/trans), protein structure levels, and nucleic acid components (pyrimidines/purines, nucleosides/nucleotides, ribose/deoxyribose, 5'/3' ends).
Phospholipids:
Structure: glycerol with two fatty acids (hydrophobic tails) and a phosphate-containing head (hydrophilic)
In water, phospholipids self-assemble into a bilayer with hydrophobic tails inward and hydrophilic heads outward
The bilayer forms the core of cell membranes
Steroids:
Lipids with a carbon skeleton of four fused rings
Cholesterol: an important membrane component in animals; essential but high levels in blood can contribute to cardiovascular disease
Summary of lipids:
Not true polymers
Hydrophobic
Important structural and energy storage roles; membranes and signaling molecules
Concept 5.4: Proteins have many structures, resulting in a wide range of functions
Proteins account for more than 50% of the dry mass of most cells
Protein functions include:
Enzymatic: catalyzing chemical reactions
Structural: support for cells and tissues (e.g., collagen, keratin)
Storage: amino acids as reservoirs
Transport: carrying substances (e.g., hemoglobin)
Hormonal and receptor signaling: coordination of activities and responses
Movement: motor proteins (e.g., actin and myosin)
Defense: antibodies protecting against disease
Table 5-1 overview of protein functions (selected examples):
Enzymatic proteins: digestive enzymes
Structural proteins: silk fibers; collagen and elastin; keratin
Storage proteins: ovalbumin, casein
Transport proteins: hemoglobin
Hormonal proteins: insulin
Receptor proteins: receptors in nerve membranes
Contractile proteins: actin and myosin
Defensive proteins: antibodies
Protein structure levels (Fig. 5-19, 5-20, 5-21):
Primary structure: unique sequence of amino acids in a protein
Secondary structure: regular coils and folds (α-helix and β-pleated sheet) formed by hydrogen bonds along the backbone
Tertiary structure: three-dimensional shape stabilized by interactions among R groups (side chains)
Quaternary structure: association of two or more polypeptide chains into a single macromolecule
Enzymes:
Proteins that act as catalysts to speed up chemical reactions
Enzymes can be reused; function as workhorses in cellular processes
Amino acids:
20 standard amino acids used to build proteins
Basic structure: amino group (–NH2), carboxyl group (–COOH), and an R group (side chain) attached to the central carbon (α-carbon)
R groups give amino acids distinctive properties (polar, nonpolar, acidic, basic; Fig. 5-UN1 and 5-17 family classifications)
Peptide bonds:
Covalent bonds linking amino acids in a chain
Formed by a dehydration reaction between the carboxyl group of one amino acid and the amino group of the next
Backbone: repeating sequence of N–Cα–C atoms; side chains (R) extend outward
Protein structure and folding (Fig. 5-21, 5-21a–g):
The amino acid sequence determines a protein’s three-dimensional structure
The structure determines the protein’s function
Case study: Sickle-cell disease (Fig. 5-22):
A single amino acid substitution in hemoglobin changes the protein’s quaternary structure and function
Normal hemoglobin vs sickle-cell hemoglobin generates different shapes and oxygen-carrying capabilities
Denaturation and renaturation:
Denaturation: loss of a protein’s native structure due to changes in pH, salt concentration, temperature, or other factors
Denatured proteins are biologically inactive
Renaturation (renaturation): some proteins can regain function when conditions return to normal
Protein folding in the cell:
Predicting a protein’s structure from its primary sequence is difficult
Proteins likely pass through several states before reaching a stable structure
Chaperonins: protein machines that assist proper folding of other proteins
Chaperonins (Fig. 5-24):
Hollow cylinder with a cap
Unfolded polypeptide enters the cylinder; cap closes and reshapes the environment to promote folding
Cap opens and the folded protein is released
Methods to determine protein structure:
X-ray crystallography: determines structure from diffraction patterns of crystallized proteins
Nuclear magnetic resonance (NMR) spectroscopy: determines structure without crystallization
Bioinformatics: uses computer programs to predict structure from amino acid sequences
Conceptual takeaway: structure–function relationship is central to understanding biology; structure emerges from sequence and cellular environment
Concept 5.5: Nucleic acids store and transmit hereditary information
Genes: units of inheritance; programs amino acid sequences of polypeptides
Nucleic acids are the polymers called polynucleotides
Two types of nucleic acids: DNA and RNA
Roles:
DNA provides directions for its own replication
DNA directs synthesis of messenger RNA (mRNA), and through mRNA, controls protein synthesis
Protein synthesis occurs in ribosomes
DNA and RNA roles in the central dogma: DNA → RNA → protein
Structure of nucleic acids:
Polynucleotides: nucleotides linked by phosphodiester bonds forming a sugar–phosphate backbone with nitrogenous bases as appendages
Each nucleotide consists of a nitrogenous base, a pentose sugar, and a phosphate group
The portion of a nucleotide without the phosphate is a nucleoside
Nucleoside and nucleotides:
Nucleoside: nitrogenous base + sugar
Nucleotide: nucleoside + phosphate group
Nitrogenous bases:
Purines: adenine (A) and guanine (G) (two-ring structures)
Pyrimidines: cytosine (C), thymine (T) (DNA), uracil (U) (RNA) (single-ring structures)
Sugars:
Deoxyribose (DNA) vs ribose (RNA)
Nucleotide polymers:
Adjacent nucleotides are joined by covalent bonds between the 3' hydroxyl of one nucleotide and the 5' phosphate of the next
Backbone: sugar–phosphate units; nitrogenous bases extend as side groups
Sequence of bases along a DNA or mRNA polymer is unique for each gene
DNA double helix:
Two polynucleotides spiraling around an axis in an antiparallel arrangement (5' → 3' and 3' → 5' directions)
Nitrogenous base pairing via hydrogen bonds: A pairs with T (or U in RNA) and G pairs with C
A–T pairs form two hydrogen bonds; G–C pairs form three hydrogen bonds
DNA as a molecular chronicle of life:
Linear nucleotide sequences are passed from parents to offspring
Two closely related species have more similar DNA than distant relatives
Molecular biology can be used to assess evolutionary relationships
Protein synthesis and gene expression are guided by nucleic acids:
DNA is transcribed to mRNA in the nucleus; mRNA is translated into proteins at ribosomes
Notable figures and terms (conceptual references):
Fig. 5-26 series: mRNA synthesis, movement to cytoplasm, ribosome involvement
Fig. 5-27 series: nucleoside, nucleotide, and polynucleotide components; end designations (5' and 3' ends)
Fig. 5-28: general comparison of sugar–phosphate backbones and base pairing
Additional themes and cross-cutting ideas
Emergent properties in the chemistry of life:
Higher levels of organization yield new properties not present at lower levels
Organization is central to the chemistry of life
Evolution and molecular biology:
DNA sequence similarity reflects evolutionary relatedness
Molecular data provide a tape measure of kinship among organisms
Quick recall check (from the review prompts):
Four major classes of macromolecules and their monomers/polymers
Glycosidic linkages: monosaccharides, disaccharides, polysaccharides
Saturated vs unsaturated fats; cis vs trans isomers; hydrogenation implications
Four levels of protein structure and how structure determines function
Pyrimidines vs purines; nucleosides vs nucleotides; ribose vs deoxyribose; 5' vs 3' ends of nucleotides
(Note: All specific examples and figures referenced in the slides are summarized to capture key concepts, relationships, and definitions relevant to Chapter 5.)
Here are some questions about proteins based on your notes:
What are the diverse roles that proteins perform in cells, and can you provide an example for each role listed in the notes?
Describe the four levels of protein structure (primary, secondary, tertiary, and quaternary) and explain what stabilizes each level.
What are amino acids, and what is their basic structure? How do R groups determine the distinctive properties of amino acids?
Explain how peptide bonds are formed and what they contribute to the protein's backbone.
What is protein denaturation, what external factors can cause it, and what happens to a denatured protein's biological activity?
How does a single amino acid substitution, as seen in sickle-cell disease, impact the structure and function of a protein like hemoglobin?
What are chaperonins, and what is their function in protein folding? Describe their mechanism.