Acids and bases are enormously important in enzyme chemistry. A thorough knowledge of acid–base chemistry is crucial to understand reaction mechanisms and catalysis. According to the Bronsted definition of acids and bases, any substance (or a functional group) that has a tendency to lose a proton is an acid. Correspondingly, a base will then be a proton (H+) acceptor. This definition, as we will see below, eminently suits our understanding of the role of acid–base groups at the enzyme active site. However, Lewis provided a broader definition of acids and bases. Accordingly, a Lewis acid is a substance that accepts an electron pair from a base while a Lewis base is a substance that donates an electron pair to an acid. Lewis acids are involved in enzyme-catalyzed processes as cofactors. Metal cations such as Mg2+, Mn2+, Zn2+, and iron–sulfur clusters are Lewis acids. One way of visualizing this acidity is to consider water molecule coordinated to Zn2+, for instance. Because a lone pair of oxygen is donated to Zn2+ (the Lewis acid), the O–H bond of bound water is better polarized and therefore more readily loses a proton (i.e., H+). While the definition of base is practically same in the two definitions, the concept of Lewis acids is much broader and goes beyond just the H+ donors.