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I see that aspirin (in part) works by inhibiting cycloxygenase isoenzymes and that this inhibiting is irreversible. I've had a few classes mentioning this topic in passing, but never with depth.

I guess my question regards the permanence of the word "irreversible." I assume enzymes have a life span, so to speak, and that the same isoenzymes both die and are being replenished at some given rate.

Am I correct in thinking that the cycloxygenase enzyme is permanently inhibited until its death (catabolism)?

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    $\begingroup$ As far as I know, aspirin is an acetylating agent,. meaning that it attaches an acetyl to a serine (via a covalent bond) inside the active site of the cycloxygenase enzyme. With the active site now being unable to used, the enzyme will die by degrading (its structure will define this time) or denaturing (due to external changes in environment), whichever occurs first. I have no sources, this is all from what I learnt a while back through textbooks and teachers, so I'm not prepared to write an answer just yet, but I hope this helps! $\endgroup$
    – Butallati
    May 2 '16 at 2:07
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    $\begingroup$ Yup. Inhibited until degradation since as @butallati mentions, they acetylated - chemically modified. In fact this irreversibility has a significance - that the enzyme can be replenished in the endothelium but not in the platelets. $\endgroup$
    – Polisetty
    May 2 '16 at 4:40
  • $\begingroup$ I had an interesting insight from a lecture: "If someone takes irreversible blockers, will you ever recover the function of the tissue? Yes. Old receptors will be catabolized and eventually new receptors will be synthesized by the tissue." So its death is from catabolism $\endgroup$
    – adnauseam
    Nov 29 '18 at 14:44
  • $\begingroup$ @adNauseam ""If someone takes irreversible blockers, will you ever recover the function of the tissue? Yes". Up to a point. If you take enough of an irreversible acetylcholine esterase inhibitor (like sarin), you won't recover the tissue function… since you'd be dead. $\endgroup$
    – Jam
    Nov 29 '18 at 17:02
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‘Reversible’ and ‘Irreversible’ are standard designations in enzyme kinetics. It may be that your instructor was using the word in this sense.

As already commented, irreversible inhibitors bind the enzyme in such a way that they don't dissociate from it. Either they form a covalent bond or their affinity for the binding site is extremely high. Reversible inhibition is generally found with competitive inhibitors — those that resemble substrate enough to bind to the active site and compete with the substrate for it. Unless they have an extremely high affinity there will be an equilibrium between bound and unbound inhibitor, and the inhibitor can be competed out by substrate — i.e. the binding is reversible.

You can read about this in more detail, but still at an introductory level, in the Wikipedia article on Enzyme Inhibitors or this section in the online version of Berg et al.

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