Enzymes and substrates
An enzyme is a biological catalyst, almost always a protein, that speeds a reaction by lowering its activation energy without being consumed. The substrate is the molecule the enzyme acts on, binding to a specific pocket called the active site.
Enzymes make metabolism possible by accelerating reactions that would otherwise proceed far too slowly at body temperature. They do this by stabilizing the transition state and thereby lowering the activation energy. Critically, an enzyme does not change the free energy difference between reactants and products or shift the position of equilibrium — it changes only how fast equilibrium is reached.
The substrate binds to the enzyme's active site, a small pocket whose shape and chemistry determine specificity. The older lock-and-key model treats the site as rigidly complementary; the more accurate induced fit model holds that binding causes a conformational change that tightens the interaction. Many enzymes require a nonprotein partner to work: metal ion cofactors such as zinc or magnesium, or organic coenzymes, many of which are vitamin derivatives — which is why vitamin deficiencies produce such specific metabolic failures.
Enzyme kinetics is usually described by the Michaelis-Menten relationship, in which reaction velocity rises with substrate concentration and then plateaus at Vmax as the enzyme becomes saturated. Km is the substrate concentration producing half of Vmax and is an inverse index of affinity: a low Km means the enzyme binds substrate tightly. Inhibitors are classified by their effect on these two constants. A competitive inhibitor resembles the substrate, binds the active site, raises Km, and leaves Vmax unchanged because excess substrate can outcompete it. A noncompetitive inhibitor binds elsewhere on the enzyme, lowers Vmax, and does not change Km. Beyond inhibition, cells regulate enzymes through allosteric effectors, covalent modification such as phosphorylation, and synthesis of inactive precursors called zymogens.
USMLE Step 1 tests this material in the biochemistry section and returns to it constantly. You should be comfortable reading a Michaelis-Menten or Lineweaver-Burk plot and naming the type of inhibition, connecting a coenzyme to its parent vitamin, and recognizing rate-limiting enzymes as the regulated steps of pathways such as glycolysis and the urea cycle. Many pharmacology items are enzyme kinetics questions in disguise, since so many drugs act as enzyme inhibitors.
Key takeaways
- Enzymes lower activation energy and speed reactions without being consumed or changing the equilibrium position.
- The substrate binds the active site, with specificity explained by the induced fit model.
- Many enzymes require metal cofactors or vitamin-derived coenzymes to function.
- Km is the substrate concentration at half Vmax and varies inversely with binding affinity.
- Competitive inhibitors raise Km without changing Vmax; noncompetitive inhibitors lower Vmax without changing Km.