Table of Contents
What Are Biological Macromolecules?
Biological macromolecules are very large molecules built by linking many smaller units (monomers) into long chains (polymers). They are the main “materials” of living cells and are responsible for most of their structure and function.
Four major classes of biological macromolecules are usually distinguished:
- Proteins
- Carbohydrates
- Lipids
- Nucleic acids
Each of these will be covered in its own chapter. Here, the focus is on what they have in common as macromolecules and what makes them special as a group.
Macromolecules are typically:
- Made of a large number (often thousands) of atoms
- Built by repeating similar building blocks
- Held together by covalent bonds in the main chain
- Organized into higher‑level structures (e.g., folding, branching, assemblies)
- Central to life’s structure (e.g., membranes, fibers) and information (e.g., DNA, RNA), and to processes (e.g., enzymes)
Monomers, Polymers, and Condensation Reactions
Monomers and Polymers
A central idea for macromolecules is the relationship between monomers and polymers:
- Monomer: a small molecule that can be linked to similar units
- Polymer: a long molecule built by joining many monomers in a chain
Examples (details in later chapters):
- Proteins: monomers = amino acids; polymer = polypeptide/protein
- Carbohydrates: monomers = monosaccharides (simple sugars); polymers = polysaccharides (e.g., starch, cellulose)
- Nucleic acids: monomers = nucleotides; polymers = DNA or RNA strands
Lipids are a special case: many important biological lipids are not strictly polymers of identical repeating monomers, but complex molecules often built from recurring components (e.g. glycerol and fatty acids). They are still treated with macromolecules because of their size and importance.
Condensation (Dehydration) Reactions
Most biological polymers are formed by condensation reactions (also called dehydration synthesis):
- Two monomers are joined
- A small molecule of water is released
- A new covalent bond is formed
In simplified form, this can be written as:
$$
\text{monomer}_1\;-\;\text{H} + \text{HO}\;-\;\text{monomer}_2
\;\longrightarrow\;
\text{monomer}_1\;-\;\text{monomer}_2 + \text{H}_2\text{O}
$$
For example:
- Two monosaccharides join to form a disaccharide + water
- An amino group of one amino acid joins the carboxyl group of another, forming a peptide bond + water
- Two nucleotides are linked via a phosphodiester bond, releasing water
Enzymes in cells catalyze these reactions and make them highly specific (only certain monomers are joined, and in a defined orientation).
Hydrolysis: The Reverse Process
The reverse of condensation is hydrolysis (“splitting with water”):
- A polymer (or dimer) is split into smaller units
- A water molecule is consumed
- The covalent bond is broken
General scheme:
$$
\text{polymer segment} + \text{H}_2\text{O}
\;\longrightarrow\;
\text{monomer}_1\;-\;\text{H} + \text{HO}\;-\;\text{monomer}_2
$$
Hydrolysis is essential for digestion and for breaking down macromolecules when their components are needed elsewhere (e.g., to recycle amino acids).
Condensation and hydrolysis together form a dynamic cycle, allowing cells to build up and break down macromolecules as needed.
General Structural Principles of Macromolecules
Although each macromolecule type has its own special features, several structural principles apply broadly.
Directionality and Sequence
Many biological polymers are directional: the two ends of the chain are chemically different. For example (details in later chapters):
- Proteins: N‑terminus (free amino group) and C‑terminus (free carboxyl group)
- Nucleic acids: 5′ end and 3′ end of the sugar‑phosphate backbone
- Some polysaccharides: reducing end and non‑reducing end
Because of this directionality, the order of monomers (sequence) along the chain matters. Different sequences, even with the same types of monomers, can lead to very different properties and functions:
- A different amino acid sequence → a different protein structure and activity
- A different nucleotide sequence → a different genetic information
Sequence is thus a key concept: it encodes information in nucleic acids and shapes structure and function in proteins and some carbohydrates.
Levels of Structure and Folding
Many macromolecules do not remain as simple, extended chains. They often:
- Fold into compact three‑dimensional shapes
- Associate with other chains
- Sometimes form complex assemblies with lipids or small molecules
Typical levels of organization (in abstract):
- Primary structure
- The linear sequence of monomers in the chain
- Higher‑order structure
- Folding and three‑dimensional arrangement within a single chain
- Assembly with other chains or molecules
This folding and assembly is driven by many weak interactions:
- Hydrogen bonds
- Ionic interactions
- Hydrophobic interactions (nonpolar parts cluster away from water)
- van der Waals forces
The three‑dimensional shape that results is crucial for function (e.g., an enzyme’s active site, a receptor’s binding pocket, the double helix of DNA).
Polymers vs. Complexes
Macromolecules can function:
- As single polymers (e.g., a single enzyme molecule)
- As complexes of several macromolecules and sometimes small components:
- Multi‑subunit proteins (several polypeptide chains)
- Nucleoprotein complexes (e.g., DNA + proteins)
- Membrane assemblies (lipids + proteins + carbohydrates)
These complexes often act as “molecular machines,” carrying out tasks such as replication, transport, or movement.
Chemical Bonds in Macromolecules
The structure of macromolecules relies on two main categories of bonds:
Covalent Bonds: The Backbone
The backbone of macromolecules is held together by covalent bonds, which are strong and stable under normal biological conditions.
Typical backbone bonds (names are covered in later chapters):
- Between sugars in carbohydrates
- Between amino acids in proteins
- Between nucleotides in nucleic acids
- Between glycerol and fatty acids or other groups in lipids
Because covalent bonds are stable, breaking or forming them usually requires specific enzymes and energy input or release.
Non‑covalent Interactions: Shape and Flexibility
The shape, folding, and interactions of macromolecules rely heavily on weaker, non‑covalent forces, including:
- Hydrogen bonds
- Stabilize helices, sheets, and base pairing
- Ionic interactions (attractions between charged groups)
- Hydrophobic interactions
- Nonpolar parts gather away from water, important in membranes and protein cores
- van der Waals forces
- Very weak, short‑range attractions that become important when many atoms are in close proximity
Although individually weaker than covalent bonds, their collective effect shapes how macromolecules fold, recognize other molecules, and form complexes. They also allow flexibility: macromolecules can change shape, which is important for their function (e.g., opening and closing of channels, switching of regulatory proteins).
Macromolecules and Water
Because life occurs in an aqueous environment, interactions between macromolecules and water are crucial.
Key aspects:
- Hydrophilic regions (polar or charged groups)
- Interact well with water, often exposed on the outside of macromolecules
- Hydrophobic regions (nonpolar groups)
- Avoid water, tend to cluster in the interior or within membranes
Consequences:
- Proteins often fold so that hydrophobic side chains are buried inside, with hydrophilic residues outside.
- Lipids can self‑assemble into bilayers and micelles, forming membranes and compartments.
- Some polysaccharides (like cellulose) form strong fibers via many hydrogen bonds, while others (like some storage polysaccharides) are more compact and water‑accessible.
The balance between hydrophilic and hydrophobic parts strongly influences solubility, location (e.g., in membranes vs. cytosol), and biological role.
Macromolecules as Functional Units in Cells
Each macromolecule class has its own specific chapter, but a few general roles can be highlighted here to show why macromolecules are central to life.
Structural Roles
Many macromolecules are part of the “architecture” of cells and organisms:
- Fibers and frameworks in cells (cytoskeleton, extracellular matrix)
- Cell walls and supportive tissues (e.g., in plants and fungi)
- Membranes that define cells and internal compartments
These structures give shape, mechanical strength, and protection.
Storage of Information and Energy
Macromolecules can store:
- Information
- Sequences of nucleotides in nucleic acids form the genetic code
- Energy and material
- Certain carbohydrates and lipids serve as energy reserves
- Some macromolecules serve as reservoirs of building blocks
The ability to store and retrieve information in a stable yet flexible form is a defining property of life and is tied to macromolecular structure.
Catalysis, Regulation, and Communication
Many processes in cells are carried out by macromolecules:
- Catalysis of biochemical reactions by specialized macromolecules (enzymes)
- Regulation of when and how strongly processes run (regulatory proteins, nucleic acids)
- Signal transmission inside and between cells (receptors, signaling molecules, and their targets)
These functions rely on the specific shapes and binding properties of macromolecules, which in turn depend on their sequences and interactions.
Diversity and Specificity of Macromolecules
Despite being built from a limited set of monomers (e.g., 20 common amino acids, 4 main DNA bases), macromolecules can show enormous diversity:
- Even a short chain of 10 amino acids can have
$^{10}$$
possible sequences. - Longer chains, and combinations into complexes, increase potential diversity far beyond what actually exists in nature.
This combinatorial richness allows:
- Highly specific binding (e.g., an enzyme recognizing one substrate)
- Very specialized functions in different cell types and organisms
- The evolution of new functions by small changes in sequence and structure
At the same time, shared types of macromolecules across all life (for example, DNA and many core proteins) reflect a common biochemical “toolkit” and evolutionary origin.
Overview and Link to Subsequent Chapters
Macromolecules thus form an integrated system:
- Built by linking small units (monomers) into long chains (polymers)
- Assembled and broken down via condensation and hydrolysis
- Shaped by covalent bonds and non‑covalent interactions
- Interacting with water to form structures like membranes and fibers
- Serving as structural materials, information carriers, catalysts, and regulators
The following chapters will examine each main class of macromolecules in detail:
- Proteins and their structure
- Carbohydrates
- Lipids
- Nucleic acids
- Other important molecules
Together, they will show how variations on a relatively simple chemical theme—chains of small building blocks—can give rise to the astonishing complexity of living systems.