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I find listed on the Sigma-Aldrich site a large list of enzymes & corresponding inhibitors. e.g. For the enzyme squalene synthase the inhibitor listed is "Zaragozic acid A trisodium salt"

Would this mean that if I added the right amount of this chemical to, say, a Yeast cell culture I might expect to get reduced activity of Squalene Synthase which is native to yeast and catalyses the transformation of FPP to Squalenes.

Would this even be a reasonable thing to try if I had a goal to block Squalene synthase? Or am I interpreting how these inhibitors ought to be used incorrectly? Can they be used with in vivo cultures at all?

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This is usually the way this kind of inhibitors are used. There needs to be a way that they come into the cells (if they stay in solution and cannot reach their target they will be useless), but then they inhibit their targets.

What usually needs to be done is to determine which concentrations are needed in the cell culture (or the medium) to be effective for the inhibition but not to harm the cells. Therefore I usually use different concentrations of the inhibitor in culture and then measure the outcome.

To find the right concentrations, see if there are some recommendations from the manufacturers. Otherwise you will probably have to dig through Pubmed to find some starting point.

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  • $\begingroup$ Thanks! Any thoughts on what concentration range might be reasonable to attempt with Zaragozic acid for inhibiting Squalene synthesis in yeast? Also, do you think yeast cells would pick it up? $\endgroup$ – curious_cat Apr 2 '16 at 19:09
  • $\begingroup$ Honestly: I have no idea. Are there any recommendations by the distibutors? Otherwise you will probably have to dig through Pubmed to find suitable concentrations. If there is nothing, you need to try it. $\endgroup$ – Chris Apr 2 '16 at 19:19

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