Biomolecules: Macromolecules and Enzymes

Micromolecules and macromolecules

A living cell is built from small, simple molecules (micromolecules, such as individual amino acids, sugars and nucleotides) and the large, complex polymers they combine to form (macromolecules). The four major classes of biological macromolecules are carbohydrates, proteins, lipids and nucleic acids. Carbohydrates range from simple monosaccharides (single sugar units, such as glucose) through oligosaccharides (a small number of linked sugar units) to polysaccharides (long chains of many linked sugar units, such as starch and cellulose), each level built by progressively joining more of the simple sugar unit together. Proteins are polymers of amino acids linked by peptide bonds, and a protein's actual three-dimensional shape, on which its biological function depends, is described at four increasingly complex levels: primary structure (the linear sequence of amino acids), secondary structure (local folding patterns such as the alpha helix and beta sheet, held by hydrogen bonding), tertiary structure (the overall three-dimensional folding of a single polypeptide chain), and quaternary structure (the arrangement of multiple folded polypeptide chains, or subunits, assembled together into one functional protein).

Enzymes: how a biological catalyst actually works

Nearly all enzymes are proteins (a small number of catalytic RNA molecules, called ribozymes, are the exception), and an enzyme's defining job is to speed up a specific biochemical reaction by lowering its activation energy, the energy barrier that must be overcome before a reaction can proceed, without itself being consumed in the reaction.

Two competing models describe how an enzyme's active site (the specific region that binds the substrate) actually interacts with its substrate. The older lock-and-key model treated the active site as a rigid shape that fits its substrate perfectly from the very start, the way a key fits a matching lock, with no meaningful change in the enzyme's own shape upon binding. The currently accepted induced fit model instead holds that the active site is flexible rather than rigid: the enzyme initially binds its substrate somewhat loosely, and the binding itself induces a conformational change in the enzyme's shape, reshaping the active site so that it grips the substrate, specifically the high-energy transition state of the reaction, much more tightly, and it is precisely this induced reshaping around the transition state that lowers the activation energy and speeds up the reaction, rather than a pre-formed, static perfect fit.

Many enzymes cannot function alone and require a non-protein helper molecule, a cofactor, to be catalytically active. Cofactors fall into two broad categories: metal ions (such as iron or magnesium, called activators when needed for activity), and organic coenzymes, generally derived from vitamins. Coenzymes themselves split further by how tightly they associate with the enzyme: a prosthetic group binds tightly and remains permanently attached to the enzyme throughout the reaction cycle, while a co-substrate (or cosubstrate) binds only loosely and temporarily, typically to transfer a chemical group onto the substrate before dissociating again, a genuinely different binding behaviour from a prosthetic group's permanent attachment.

Enzyme classification: six classes by reaction type

Enzymes are formally classified into six major classes based purely on the type of chemical reaction they catalyse, a classification system worth holding as a fixed list: oxidoreductases (catalyse oxidation-reduction reactions), transferases (transfer a functional group from one molecule to another), hydrolases (catalyse hydrolysis, breaking a bond using water), lyases (break a bond to form two products without using water), isomerases (convert a molecule into one of its own structural isomers), and ligases (join two molecules together into one, typically using energy from ATP).

Quick revision points

• Macromolecules: carbohydrates (monosaccharides to oligosaccharides to polysaccharides), proteins (amino acids joined by peptide bonds), lipids, nucleic acids.
• Protein structure levels: primary (amino acid sequence), secondary (local folding, e.g. alpha helix, beta sheet), tertiary (overall 3D fold of one chain), quaternary (assembly of multiple folded chains/subunits).
• Enzymes lower a reaction's activation energy without being consumed. Lock-and-key model: rigid active site, perfect pre-formed fit. Induced fit model (currently accepted): flexible active site reshapes around the substrate/transition state upon binding, and that reshaping is what lowers activation energy.
• Cofactors: metal ions (e.g. iron, magnesium) and coenzymes (vitamin-derived); coenzymes split into prosthetic groups (bind tightly, stay attached throughout the reaction) and co-substrates (bind loosely, transfer a group, then dissociate).
• Six enzyme classes by reaction type: oxidoreductases (oxidation-reduction), transferases (group transfer), hydrolases (hydrolysis), lyases (bond-breaking without water), isomerases (isomer conversion), ligases (joining two molecules, using ATP energy).