Background: Several steps of eukaryotic coenzyme Q biosynthesis are still in question. Results: Yeast coq null mutants overexpressing the Coq8 kinase have stable Coq polypeptides and accumulate new Q intermediates that help diagnose the blocked step. Conclusion: New functions for Coq polypeptides are proposed. Significance: Identification of the blocked step allows for the use of alternate ring precursors that rescue Q biosynthesis in some mutants.
Coenzyme Q (ubiquinone or Q) is a lipid electron carrier in the electron transport chain. In yeast Saccharomyces cerevisiae nine genes, designated COQ1 through COQ9, have been identified as being required for Q biosynthesis. Generally, 4‐hydroxybenzoic acid (4‐HB) is considered the aromatic ring precursor to Q biosynthesis. Recently, para‐aminobenzoic acid (pABA), a well‐known precursor of folate, has been discovered as an alternative ring precursor to Q biosynthesis in yeast. This was a surprising finding because folate is synthesized de novo from pABA in yeast, but is a vitamin for human. In this study, we find pABA is also an aromatic ring precursor in Q biosynthesis in mammalian cells. We utilize liquid chromatography and mass spectrometry (LC‐MS/MS), and show that human and murine cells labeled with 13C6‐pABA synthesize 13C6‐Q. This work was supported by National Science Foundation Grant 0919609, National Institutes of Health (NIH) Grant GM45952, and Ruth L. Kirschstein National Research Service Award GM007185. The LC‐MS/MS determination of Q content was supported by Grant Number S10RR024605 from the National Center for Research Resources.
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