Impact of Chemical Analogs of 4-Hydroxybenzoic Acid on Coenzyme Q Biosynthesis: From Inhibition to Bypass of Coenzyme Q Deficiency.

Abstract

Coenzyme Q is a lipid that participates to important physiological functions. Coenzyme Q is synthesized in multiple steps from the precursor 4-hydroxybenzoic acid. Mutations in enzymes that participate to coenzyme Q biosynthesis result in primary coenzyme Q deficiency, a type of mitochondrial disease. Coenzyme Q10 supplementation of patients is the classical treatment but it shows limited efficacy in some cases. The molecular understanding of the coenzyme Q biosynthetic pathway allowed the design of experiments to bypass deficient biosynthetic steps with analogs of 4-hydroxybenzoic acid. These molecules provide the defective chemical group and can reactivate endogenous coenzyme Q biosynthesis as demonstrated recently in yeast, mammalian cell cultures, and mouse models of primary coenzyme Q deficiency. This mini review presents how the chemical properties of various analogs of 4-hydroxybenzoic acid dictate the effect of the molecules on CoQ biosynthesis and how the reactivation of endogenous coenzyme Q biosynthesis may achieve better results than exogenous CoQ10 supplementation.

• Authors: Fabien Pierrel
• Journal: Frontiers in physiology (Front Physiol) Vol. 8 Pg. 436 ( 2017) ISSN: 1664-042X [Print] Switzerland
• PMID: 28690551 (Publication Type: Journal Article, Review)