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Studies into the synthetic analogs of key intermediates, and ring precursors in the biosynthetic pathway of Coenzyme Q: Synthesis and metabolism
Author(s) -
Nag Anish,
He Cuiwen,
Shepherd Jennifer N,
Fernandez Lucia,
Clarke Catherine F,
Villalba Jose M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.661.7
Subject(s) - biosynthesis , prenylation , biochemistry , stereochemistry , enzyme , coenzyme q – cytochrome c reductase , chemistry , biology , mitochondrion , cytochrome c
Coenzyme Q (ubiquinone or Q) is a redox active lipid molecule, with a fully substituted benzoquinone ring and a polyisoprenoid tail, containing up to ten isoprene units. Q is an essential component of the mitochondrial respiratory electron transport chain. The exact biosynthetic pathway has still not been completely characterized. In this study, farnesylated analogs of several Q intermediates have been been chemically synthesized. The synthesis of 2‐farnesyl‐1,4‐hydroquinone serves as an analog of 3‐hexaprenyl‐4‐hydroxyphenol, which accumulates in yeast coq6 and coq9 mutants that over‐express the Coq8 polypeptide. In addition farnesylated analogs of 5‐demethoxy‐Q 3 (DMQ 3 ), 2‐demethyl‐5‐demethoxy‐Q 3 (DDMQ 3 ), and 2‐demethyl‐5‐demethoxy‐4‐amino‐Q 3 (IDDMQ 3 H 2 ) were chemically synthesized. The farnesylated analogs are added to yeast cell cultures to determine whether they serve as precursors and/or intermediates in the biosynthesis of Q 3 . Also, other selected farnesylated substrates such as 3‐farnesyl‐4‐hydroxybenzoic acid, 3‐farnesyl‐4,5‐dihroxybenzoic acid and others are being synthesized for studying Q metabolism. These substrates can also serve as ligands in protein binding assays and as substrates with isolated enzymes. In addition, a number of different compounds are being tested in assays with mammalian cells, to analyze their roles as ring precursors for Q biosynthesis. Thereby we hope to understand and further characterize the biosynthetic and metabolic pathways responsible for Q biosynthesis and function in different living systems. Support or Funding Information This research was funded by NSF MCB‐1330803