Para-aminobenzoic Acid is an Alternative Aromatic Ring Precursor of Coenzyme Q Biosynthesis in Mammalian Cells

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.