Hydrolysis, biotransformation reaction class

Another therapeutic class to be briefly discussed is that of the lipid-lowering agents known as fibrates, e.g., clofibrate and fenofibrate (8.5). Here also, the acidic metabolite is the active form clofibrate (an ethyl ester) is rapidly hydrolyzed to clofibric acid by liver carboxylesterases and blood esterases [11], Human metabolic studies of fenofibrate (8.5), the isopropyl ester of fenofibric acid, showed incomplete absorption after oral administration, while hydrolysis of the absorbed fraction was quantitative [12], This was followed by other reactions of biotransformation, mainly glucuronidation of the carboxylic acid group. 

The metabolic degradation of local anesthetics depends on whether the compound has an ester or an amide linkage. Esters are extensively and rapidly metabolized in plasma by pseudochoUnesterase, whereas the amide linkage is resistant to hydrolysis. The rate of local anesthetic hydrolysis is important, since slow biotransformation may lead to drug accumulation and toxicity. In patients with atypical plasma cholinesterase, the use of ester-linked compounds, such as chloroprocaine, procaine and tetracaine, has an increased potential for toxicity. The hydrolysis of all ester-linked local anesthetics leads to the formation of paraaminobenzoic acid (PABA), which is known to be allergenic. Therefore, some people have allergic reactions to the ester class of local anesthetics. 

During the biotransformations affecting xenobiotics, five major kinds of chemical reactions may occur oxidations (by far the most important), reductions, hydrolysis, substitutions, and eliminations. As Phase I and II reactions are part of this classification, each class of reactions can give rise to toxic metabolites. 

According to the Warwick Biotransformation Club Database in 1987/88 [60], approximately 65% of all applications reported fell into the classes of esterolytic reactions (ester hydrolysis, synthesis or transesterification) (40%) and dehydrogenase reactions (25%). Next in importance were oxygenase-mediated reactions, peptide and oligosaccharide synthesis, which together comprise 24% of the total. Reports of enzymatic procedures for carbon-carbon bond formation were very few in number (2%). All other reaction types comprised less than 10% of the total. 

The biotransformation of xenobiotics is catalysed by a number of enzymes that be divided into classes of reactions. These are hydrolysis, reduction, oxidation, conjugation. These reactions are part of the current curriculum and therefore provide an opportunity for connecting chemistry and toxicology. 

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