2.1 Enzymes and Metabolic Pathways

In the induced-fit model, substrate binding causes a small conformational change in the enzyme. This change brings catalytic groups into effective positions, strains particular substrate bonds, excludes water where necessary, or stabilizes charge in the transition state. An enzyme–substrate complex forms temporarily; products then have less affinity for the active site, leave, and the enzyme is available for another cycle.

Reactants must reach an unstable transition state before products can form. The required input is the activation energy. An enzyme provides an alternative reaction route with a lower activation energy, increasing the fraction of collisions that lead to reaction. It does not change the energy difference between reactants and products, shift the equilibrium position, supply energy to an endergonic reaction, or become consumed.

At low temperature, enzyme and substrate molecules have less kinetic energy, collide less often and form fewer enzyme–substrate complexes per second. Warming initially increases collision frequency and the proportion of collisions energetic enough to react. Beyond an optimum, heat disrupts interactions that maintain tertiary structure. The active site loses complementarity and the enzyme becomes denatured. This produces the characteristic asymmetric curve: a gradual rise followed by a steep fall.

The optimum is adapted to context, not fixed at 37 °C. Many human enzymes work fastest near body temperature, while enzymes from thermophilic microorganisms remain stable at much higher temperatures. Cooling usually slows enzymes without permanently denaturing them. High temperature may irreversibly alter structure, although the exact degree depends on exposure time and the particular protein.

Changing pH changes the ionization of amino-acid side chains. Altered charges can disrupt ionic interactions and hydrogen bonding, change tertiary structure, or prevent substrate binding and catalysis directly within the active site. Each enzyme has a pH range and optimum related to its environment. A stomach protease and a cytosolic enzyme therefore need not share the same optimum.

With a fixed enzyme concentration, increasing substrate concentration raises rate at first because active sites spend less time empty. Eventually nearly every active site is occupied whenever it becomes available. Enzyme concentration is then limiting and the rate approaches a maximum. Adding more substrate cannot make each enzyme complete its catalytic cycle faster; adding enzyme can raise the maximum if other conditions remain suitable.