Metabolism normally takes place at specific regions of a molecular skeleton. If a drug is to be orally active, it should be both chemically and metabolically stable. Certain functional groups are likely to be too unstable for use in drugs. Chemically reactive functional groups, such as acid chlorides or acid anhydrides, are quickly hydrolyzed in water, and have no role in drug design. Metabolic blocking involves the placement of a metabolically stable atom at that position in order to prevent metabolism. Sometimes, drug metabolism can be prevented by removing or replacing a susceptible group. Steric shields are frequently used to protect susceptible groups such as esters and amides from hydrolysis. Usually, a bulky substituent, such as a methyl group, is added to the molecular skeleton so that it is close to the ester or amide and prevents enzymes attacking the carbonyl group.