title: Resveratrol and para-coumarate serve as ring precursors for coenzyme Q biosynthesis.
abstract: Coenzyme Q (Q or ubiquinone) is a redox-active polyisoprenylated benzoquinone lipid essential for electron and proton transport in the mitochondrial respiratory chain. The aromatic ring 4-hydroxybenzoic acid (4HB) is commonly depicted as the sole aromatic ring precursor in Q biosynthesis despite the recent finding that para-aminobenzoic acid (pABA) also serves as a ring precursor in Saccharomyces cerevisiae Q biosynthesis. In this study, we employed aromatic (13)C6-ring-labeled compounds including (13)C6-4HB, (13)C6-pABA, (13)C6-resveratrol, and (13)C6-coumarate to investigate the role of these small molecules as aromatic ring precursors in Q biosynthesis in Escherichia coli, S. cerevisiae, and human and mouse cells. In contrast to S. cerevisiae, neither E. coli nor the mammalian cells tested were able to form (13)C6-Q when cultured in the presence of (13)C6-pABA. However, E. coli cells treated with (13)C6-pABA generated (13)C6-ring-labeled forms of 3-octaprenyl-4-aminobenzoic acid, 2-octaprenyl-aniline, and 3-octaprenyl-2-aminophenol, suggesting UbiA, UbiD, UbiX, and UbiI are capable of using pABA or pABA-derived intermediates as substrates. E. coli, S. cerevisiae, and human and mouse cells cultured in the presence of (13)C6-resveratrol or (13)C6-coumarate were able to synthesize (13)C6-Q. Future evaluation of the physiological and pharmacological responses to dietary polyphenols should consider their metabolism to Q.
authors: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors: Letian X
authors: LX
authors: Xie
authors: Departments of Microbiology, Immunology, and Molecular Genetics University of California, Los Angeles, CA 90095-1569.
authors: Kevin J
authors: KJ
authors: Williams
authors: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors: Cuiwen H
authors: CH
authors: He
authors: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors: Emily
authors: E
authors: Weng
authors: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors: San
authors: S
authors: Khong
authors: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors: Tristan E
authors: TE
authors: Rose
authors: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors: Ohyun
authors: O
authors: Kwon
authors: Departments of Microbiology, Immunology, and Molecular Genetics University of California, Los Angeles, CA 90095-1569 Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095-1569.
authors: Steven J
authors: SJ
authors: Bensinger
authors: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors: Beth N
authors: BN
authors: Marbois
authors: Department of Chemistry and Biochemistry and the Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569.
authors: Catherine F
authors: CF
authors: Clarke
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003373:Coumaric Acids / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D051379:Mice; D011422:Propionates; D000077185:Resveratrol; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013267:Stilbenes / Q000378:metabolism*; D014451:Ubiquinone / Q000096:biosynthesis* / Q000737:chemistry*
chemical_list: D003373:Coumaric Acids; D011422:Propionates; D013267:Stilbenes; D014451:Ubiquinone; C495469:p-coumaric acid; D000077185:Resveratrol
keywords: antioxidants; isoprenoids; lipids/chemistry; mass spectrometry; mitochondria; plant polyphenols; stilbene; ubiquinone