ABSTRACT

The highest hydrolytic activity is in the liver, but the enzyme pseudocholinesterase is found in the serum. Gut bacteria also contain hydrolytic enzymes. Esterases that contribute to human drug metabolism fall into three major classes: the cholinesterases, carboxylesterase, and paraoxonase. Subsequent hydrolysis of the acetylated species regenerates active enzyme and acetic acid. The contribution of pseudocholinesterase, also known simply as cholinesterase, to drug metabolism is much greater as it possesses considerably broader substrate selectivity. In addition to acetylcholine, it will hydrolyze other choline esters like the muscle relaxant succinylcholine. A number of proteolytic enzymes are excreted into the digestive tract to affect the hydrolysis of ingested proteins and break them down into their constitutive amino acids. The observation of a dihydrodiol has been taken as proof that an epoxide is the precursor metabolite. Glucuronide conjugates can involve a wider variety of functional groups and many of these conjugates can also be hydrolyzed back to the parent drugs.