I have had some further thoughts after my previous question regarding the buccal delivery of medication. The active compound in aspirin (acetylsalicylic acid or systematically 2-Acetoxybenzoic acid) is salicylic acid (2-hydroxybenzoic acid).

I understand that the hydrolysis reaction occurs as follows within the stomach - therefore in the body it is an acid hydrolysis:

Hydrolysis of aspirin

N.B. The H2O is not shown in the diagram.

However having done this experimentally I know that in the lab to ensure a decent yield of salicylic acid I had to reflux the solution for several hours. Yet the onset of action of aspirin tablets is much faster than this. To me this suggests some enzymatic activity, but I have no idea which enzyme this is likely to be.

To follow on directly from my previous question, if the aspirin is absorbed directly into the bloodstream bypassing the stomach then what causes the hydrolysis in the blood stream and is it the same factor that increases the rate of hydrolysis in the stomach if the medication were to be taken orally?

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    $\begingroup$ As a side question, how are you doing all this lab work as an A-level student? V. impressive! $\endgroup$ – Rik Smith-Unna Feb 11 '12 at 11:07
  • $\begingroup$ @RichardSmith I'm lucky enough to be on a really obscure chemistry exam board - OCR Salters. It's the most practically based since Nuffield bit the dust. We have to do an extended lab project over a few months, which is a great opportunity for us! $\endgroup$ – Rory M Feb 11 '12 at 18:30

Acetylsalicylate deacetylase is the enzyme responsible for this reaction.

Precisely, the present investigation reveals that the hydrolysis of aspirin in liver, kidney and probably other tissues of rats is catalyzed by two highly substrate specific microsomal esterases, ASA esterase I and II active at acidic and slightly alkaline pH, respectively. The findings that ASA esterases have distinct organ distribution pattern and display responses to various inhibitors/activators that are different in many respects from those exhibited by cholinesterase and nonspecific carboxylesterase suggest that the latter esterases probably do not play a significant role in the hydrolysis of aspirin.

From: Ali B, Kaur S (1983) Mammalian tissue acetylsalicylic acid esterase(s): identification, distribution and discrimination from other esterases. J Pharmacol Exp Ther,226,589-594

  • $\begingroup$ That's an interesting one - according to the handbook of enzymes notably page 357, the enzyme doesn't seem adapted for use in the human stomach. This suggests that it is active elsewhere - a website suggested the liver. Does anyone know if this is the case (as it would prove an answer to how the hydrolysis happens in the bloodstream)? $\endgroup$ – Rory M Feb 11 '12 at 11:08
  • $\begingroup$ @RoryM See my update with a quote from the article. Much of the drug metabolism that the body does happens in the liver anyway, after all these are just safe dosages of "toxins" that we take for our health! $\endgroup$ – jonsca Feb 11 '12 at 11:10
  • $\begingroup$ However in Alexander's Answer to the linked question he states one advantage of buccal delivery as the bypassing of the liver. As this method supposedly gives faster delivery of the medication there must be another factor at play somewhere =) $\endgroup$ – Rory M Mar 3 '12 at 12:43
  • $\begingroup$ See en.wikipedia.org/wiki/First_pass_effect. First pass effect is just that, the reduction in the amount of absorption when the drug is first metabolized. One's blood volume makes many more subsequent passes through your liver. The article also notes the kidney as a location of the enzyme, which is just as likely to revisit the same blood volume. $\endgroup$ – jonsca Mar 3 '12 at 13:02
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    $\begingroup$ I don't want to go too far out on a limb here, because I don't know for sure, but there are probably non-specific enzymes that metabolize the ASA directly in first-pass, either by oxidation (e.g., the p450s) or conjugation (the various transferases) which render it inert. The liver is a complicated machine, and I regret that I don't remember more about first pass metabolism. $\endgroup$ – jonsca Mar 3 '12 at 13:20

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