عنوان

Investigation of the roles of Coq8p, a putative kinase, and alternate ring precursors in coenzyme Q biosynthesis

Number

TL89b7p4mr

.Language of Text, Soundtrack etc

انگلیسی

Title Proper

Investigation of the roles of Coq8p, a putative kinase, and alternate ring precursors in coenzyme Q biosynthesis

General Material Designation

[Thesis]

First Statement of Responsibility

Xie, Letian

Subsequent Statement of Responsibility

Clarke, Catherine F

Name of Publisher, Distributor, etc.

UCLA

Date of Publication, Distribution, etc.

2014

Body granting the degree

UCLA

Text preceding or following the note

2014

Text of Note

Coenzyme Q (ubiquinone or Q) is an essential redox-active, polyisoprenylated benzoquinone lipid essential for electron and proton transport in the mitochondrial respiratory chain. Eleven genes products, Coq1-Coq9, Yah1 and Arh1, are required for Q biosynthesis in yeast Saccharomyces cerevisiae. Chapter 2 details the investigation of the biological function of Coq8 and its human homolog ADCK3. Expression of ADCK3 harboring an amino-terminal yeast mitochondrial leader sequence successfully rescued growth of coq8 mutants on non-fermentable carbon source, partially restored Q biosynthesis and the phosphorylation states of Coq3, Coq5, and Coq7. Chapter 3 investigates the use of over-expression of COQ8 as a tool to study Q biosynthesis pathway in S. cerevisiae. Over-expression of the Coq8 protein restores the steady state levels of the unstable Coq proteins. This stabilization results in the accumulation of several novel Q6 biosynthetic intermediates. Several of the new intermediates contain a C4-amine and provide information on the deamination reaction that takes place when para-aminobenzoci acid is used as a ring precursor in Q biosynthesis. Chapter 4 studies the use of para-aminobenzoic acid, and resveratrol as alternative aromatic ring precursors in Q biosynthesis in E. coli, S. cerevisiae, mouse and human cells. In contrast to S. cerevisiae, neither E. coli nor mammalian cells could utilize pABA as ring precursors in Q biosynthesis. However, E. coli cells labeled with 13C6-pABA generated several novel N-containing early intermediates, suggesting UbiA, UbiD,X, and Ubil are capable of using pABA as substrates. E. coli, S. cerevisiae, human and mouse cells cultured in the presence of 13C6-resveratrol were able to synthesize 13C6-Q. Thus, future evaluation of the physiological and pharmacological responses to dietary polyphenols should consider their metabolism to Q.

Xie, Letian

Clarke, Catherine F

UCLA

Electronic name

p

[Thesis]

276903

a

Y