Yeast bioassay for identification of inositol depleting compounds

Daobin Ding, Yihui Shi, Galit Shaltiel, Abed N. Azab, Ervin Pullumbi, Adam Campbell, Dhara V. Mehta, Galila Agam, Miriam L. Greenberg

    Research output: Contribution to journalArticlepeer-review

    1 Scopus citations


    Bipolar affective disorder is a chronic, severe, debilitating illness affecting 12% of the population. Valproate, along with lithium and carbamazepine, are the only drugs for which long-term efficacy has been established. However, these drugs are ineffective for, and not well tolerated by, a large number of patients and are also associated with teratogenicity and reproductive defects. Therefore, there is a substantial need to develop more effective anti-bipolar drugs. We have previously shown that valproate, like lithium, decreases intracellular inositol, which supports the inositol depletion hypothesis. We employed inositol depletion in yeast as a screening tool to identify potential new anti-bipolar medications. We show here that hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, ethylhexanoate, and methyloctanoate decrease intracellular inositol levels and increase the expression of INO1, the gene encoding myo-inositol-3-phosphate synthase (MIPS). Similar to valproate, these inositol-depleting carboxylic acids inhibited MIPS indirectly. A correlation was shown between cell growth inhibition and the increase in INO1 expression by the carboxylic acids, factors that were reversed in the presence of inositol. Inositol depletion in yeast may be exploited as an easy and inexpensive screening test for potential new inositol depleting anti-bipolar drugs.

    Original languageEnglish
    Pages (from-to)893-899
    Number of pages7
    JournalWorld Journal of Biological Psychiatry
    Issue number4 PART 3
    StatePublished - 1 Dec 2009


    • Bipolar affective disorder
    • Inositol
    • Myo-inositol-1-phosphate synthase and carboxylic acids
    • Valproate

    ASJC Scopus subject areas

    • Psychiatry and Mental health
    • Biological Psychiatry


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