ubiquinone and 4-hydroxybenzaldehyde

Coenzyme Q (Q) is a redox lipid that is central for the energetic metabolism of eukaryotes. The biosynthesis of Q from the aromatic precursor 4-hydroxybenzoic acid (4-HB) is understood fairly well. However, biosynthetic details of how 4-HB is produced from tyrosine remain elusive. Here, we provide key insights into this long-standing biosynthetic problem by uncovering molecular details of the first and last reactions of the pathway in the yeast Saccharomyces cerevisiae, namely the deamination of tyrosine to 4-hydroxyphenylpyruvate by Aro8 and Aro9, and the oxidation of 4-hydroxybenzaldehyde to 4-HB by Hfd1. Inactivation of the HFD1 gene in yeast resulted in Q deficiency, which was rescued by the human enzyme ALDH3A1. This suggests that a similar pathway operates in animals, including humans, and led us to propose that patients with genetically unassigned Q deficiency should be screened for mutations in aldehyde dehydrogenase genes, especially ALDH3A1.

Topics: Aldehyde Dehydrogenase; Benzaldehydes; Biosynthetic Pathways; Gene Deletion; Gene Expression Regulation, Fungal; Humans; Oxidation-Reduction; Parabens; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Tyrosine; Ubiquinone

Topics: Aldehydes; Benzaldehydes; Benzoates; Carbon Isotopes; Metabolism; Parabens; Phenylacetates; Quinones; Radiometry; Research; Rhodospirillum; Rhodospirillum rubrum; Spectrum Analysis; Ubiquinone

Topics: Aldehydes; Azotobacter; Azotobacter vinelandii; Benzaldehydes; Benzoates; Benzoquinones; Carbon Isotopes; Chromatography; Hydroxybenzoates; Kidney; Metabolism; Pharmacology; Rats; Research; Saccharomyces; Saccharomyces cerevisiae; Tyrosine; Ubiquinone

Topics: Aldehydes; Benzaldehydes; Benzoquinones; Metabolism; Research; Rhodospirillum; Rhodospirillum rubrum; Ubiquinone