Aspirin esterase

Acetylsalicylate deacetylase Aspirin esterase, aspirin hydrolase Acetyl esters of aryl alcohols, negatively charged esters... 

Adebayo, G. I., Williams, J., Healy, S. Aspirin Esterase Activity Evidence for Skewed Distribution in Healthy Volunteers. Eur. J. Intern. Med. 2007,18, 299-303. 

Aspirin serum esterase activity is species dependent.194 In man it is sex linked since it was found to be higher in men than women.195 It also seems to be age dependent.196... 

Y. Kurono, H. Yamada, K. Ikeda, Effects of Drug Binding on the Esterase-Like Activity of Human Serum Albumin. V Reactive Site towards Substituted Aspirins , Chem. Pharm. Bull. 1982, 30, 296 - 301. 

Salicylic acid is a simple organic acid with a pKa of 3.0. Aspirin (acetylsalicylic acid ASA) has a pKa of 3.5 (see Table 1-3). The salicylates are rapidly absorbed from the stomach and upper small intestine yielding a peak plasma salicylate level within 1-2 hours. Aspirin is absorbed as such and is rapidly hydrolyzed (serum half-life 15 minutes) to acetic acid and salicylate by esterases in tissue and blood (Figure 36-3). Salicylate is nonlinearly bound to albumin. Alkalinization of the urine increases the rate of excretion of free salicylate and its water-soluble conjugates. 

Despite the presence of water throughout the body, hydrolysis reactions of esters and amides require enzymes to proceed at an appreciable rate. Numerous enzymes throughout the body carry out hydrolysis reactions. The enzymes, both esterases and amidases, are found in the digestive system, individual cells, and plasma. The exact site of hydrolysis of a specific drug depends on the drug s structure and functionality. The ester in aspirin... 

Drugs are known that are only active because they are metabolized to bioactive chemical species. An intrinsically active drug is frequently converted to an active metabolite. Well-known examples are the hydrolysis of aspirin to salicylic acid by esterase enzymes, the cleavage of the ethyl ether group of phenacetin to acetaminophen, the demethylation of imipramine to desipramine, and the oxidation of phenylbutazone to oxyphenbutazone. In some cases the precursor drug and its metabolite are both used therapeutically. 

Acetylsalicylic acid, or aspirin, is a white powder that is stable in a dry environment but that is hydrolyzed to salicylic acid and acetic acid under humid or moist conditions. Hydrolysis also can occur when aspirin is combined with alkaline salts or with salts containing water of hydration. Stable aqueous solutions of aspirin are thus unobtainable despite the addition of modifying drugs that tend to decrease hydrolysis. Aspirin is rapidly absorbed largely intact from the stomach and upper small intestine on oral administration but is rapidly hydrolyzed by plasma esterases. 

Aspirin. In a study, 12 healthy subjects were given a single 900-mg dose of aspirin before, during and/or after oseltamivir 75 mg twice daily for 9 doses. There was no pharmacokinetic interaction between aspirin and oseltamivir. A possible interaction was postulated since both drugs are hydrolysed by esterases and secreted by anionic tubular secretion. ... 

Both metabolism and storage of fats involve hydrolysis of the ester linkages by esterases (see A Word about Prostaglandins, Aspirin, and Pain" in Chapter 1 5) in the gut to give glycerol and fatty acids. 

A variation on the basic hydrolysis process is transesterifl-cation which is a widespread process in biological systems (c.f. the action of aspirin, choline esterase inhibitors and phosphorylation of proteins) but can also occur in vitro. In this case, the ester transfers the acyl group to the base carrying out the hydrolysis. Thus, for instance, if the base is paracetamol, as has been observed in mixtures of aspirin and paracetamol, acetylated paracetamol is produced (Fig. 5.38). 

The acyl group from an ester can be transferred to another alcohol group via the process of transesterilication. Aspirin is the most widely used dmg in which the ester group is partly responsible for its mechanism of action. In common with the acetylcholine esterase inhibitors discussed below, the target is a serine residue in the enzyme cydooxygenase 1 (COX-1). However, in the case of aspirin the covalent modification of the enzyme is irreversible. Acetylation of COX-1 prevents the production of prostaglandin inflammatory mediators. The salicylate portion of the molecule also possesses anti-inflammatory aaion (Fig. 5.46). 

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