Coq6 hydroxylase: unmasked and bypassed

Abstract

Coenzyme Q is a polyisoprenylated benzoquinone lipid essential in cellular energy metabolism. Ozeir et al. (2011) show that an enzyme, Coq6, is required for the coenzyme Q C5-ring hydroxylation, and that defects in Coq6 can be bypassed by providing alternate ring precursors.

Figure 1. Many paths to Q in yeast

S. cerevisiae utilize 4-hydroxybenzoic acid (4-HB) and para-aminobenzoic acid (pABA) as ring precursors in the synthesis of Q₆H₂ (Marbois, et al., 2010; Pierrel, et al., 2010). Coq2 attaches the polyisoprenyl tail (designated as R; in S. cerevisiae hexaprenyl-diphosphate), generating 3-hexaprenyl-4-hydroxybenzoic acid (HHB) and 3-hexaprenyl-4-aminobenzoic acid (HAB). The 4-HB and pABA pathways are speculated to converge at the point of 4-amino-DMQ₆H₂ to demethoxy-Q₆H₂ (DMQ₆H₂) (Marbois, et al., 2010). The studies of (Ozeir, et al., 2011) show that 3-hexaprenyl-4-aminophenol (4-AP) and 3-hexaprenyl-4-hydroxyphenol (4-HP) accumulate in yeast coq6 and yah1 mutants fed pABA and 4-HB, respectively (compounds denoted by red astericks). The coq6 or yah1 defect in Q biosynthesis can be bypassed by feeding the alternate ring precursors, 3,4-dihydroxybenzoic acid (3,4-diHB) or vanillic acid (VA) (compounds denoted in green).

Figure 2. The S. cerevisiae Coq6 monooxygenase requires an additional electron transport system

Coq6 is shown to work in conjunction with Yah1 (ferredoxin) and Arh1 (ferredoxin reductase).