When faced with such a high barrier, it helps to break the uphill slog into steps. Catalysts (enzymes included) employ this strategy, breaking a reaction into one or more steps.*
Linus Pauling, that greatest of American chemists, introduced the profound notion that enzymes work by stabilizing tipping points (transition state energies in the parlance) and thereby speed things up:
*The 2010 Nobel prize was awarded to three inventors of a family of very similar catalysts.