Molecules: You'd better learn to live with them.
As a followup to the entry earlier today, here is a drug that is used in the treatment of gout: allopurinol.
In vivo, purines are metabolized by the enzyme xanthine oxidase to hypoxanthine and xanthine, which are converted to uric acid:
Allopurinol is a hypoxanthine mimic, which is oxidized by xanthine oxidase to alloxanthine, which is very tightly bound to xanthine oxidase.
Tie up xanthine oxidase, purines don't get metabolized to hypoxanthine and xanthine, and you don't end up with much uric acid.
Where do all the purines go? It turns out that catabolism isn't all your body can do with wayward purines. Having gone to so much effort to synthesize them, evolution has wisely provided you with "salvage pathways" to bring the purines back into the game.
Throwing a wrench into a metabolic pathway with a substrate mimic for an enzyme is a key strategy for lots and lots of drugs. One problem with drug design is that not all pathways are "druggable" with small molecules - hence some of the interest in techniques like RNA interference, which garnered the medicine Nobel this year.
Comments
Cf: Finasteride (Proscar and Propecia), anti-androgen that takes out dihydrotestosterone anabolism, for prostate problems and to promote hair growth. Original doses were, in retrospect, immense. There is enzyme fast reversible inhibition and slow suicide inhibition. The doses was drastically cut (but not the price). Add a couple of weeks and a little dab'll do ya.
Posted by: Uncle Al | November 21, 2006 12:33 PM
Allopurinol had psychoactive effects on my dad, which other gout meds didn't have. Made him kinda nutty. Any idea what the mechanism might be?
Posted by: Jon H | December 2, 2006 8:33 PM