Another reason why covalent contalisis might take place is because once we attach this group onto the active side, that orients that group in just the proper orientation for the next step in the reaction to actually take place. So many biological reactions involve two or more substrate molecules. And this implies that for a reaction to actually take place, they must be close enough and must also have the proper orientation. And what active sites of enzymes provide is they provide that small region of space, that microenvironment that brings the substrate close enough for the collisions to actually take place at a high enough frequency. In addition, the active sites may also orient the molecules in the proper orientation for that bond to actually form and for us to form those products. Now, method number three is called acid based catalysis.