|
" Investigation of the roles of Coq8p, a putative kinase, and alternate ring precursors in coenzyme Q biosynthesis "
Xie, Letian
Clarke, Catherine F
| Document Type
|
:
|
Latin Dissertation
|
| Language of Document
|
:
|
English
|
| Record Number
|
:
|
905172
|
| Doc. No
|
:
|
TL89b7p4mr
|
| Main Entry
|
:
|
Xie, Letian
|
| Title & Author
|
:
|
Investigation of the roles of Coq8p, a putative kinase, and alternate ring precursors in coenzyme Q biosynthesis\ Xie, LetianClarke, Catherine F
|
| College
|
:
|
UCLA
|
| Date
|
:
|
2014
|
| student score
|
:
|
2014
|
| Abstract
|
:
|
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.
|
| Added Entry
|
:
|
Clarke, Catherine F
|
| Added Entry
|
:
|
UCLA
|
| |