Biosynthesis of Ubiquinone

Olson, Robert E.; Rudney, Harry

doi:10.1016/s0083-6729(08)60431-8

Cited by 159 publications

(120 citation statements)

References 175 publications

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“…Thus it is tempting to speculate that these genes are required for the related but distinct decarboxylation step in yeast Q 6 biosynthesis (Figure 1). There is evidence that decarboxylases acting in yeast Q biosynthesis may be promiscuous with regard to substrates [31]. However, yeast null mutants lacking either pad1 or ydr539w, or null mutants lacking both pad1 and ydr539w, have Q 6 levels comparable to wild-type yeast [23].…”

Section: Discussionmentioning

confidence: 99%

“…However, UbiD and UbiX polypeptides were not identified as binding partners in a global protein interaction screen [30]. Yeast and E. coli Q biosynthetic pathways are proposed to branch at the decarboxylation step (Figure 1), suggesting that the decarboxylases in the two species recognize different substrates [31]. Thus, it seems unlikely that yeast Pad1 would be able to substitute for E. coli UbiX and form a Pad1p/UbiD protein complex.…”

Section: Discussionmentioning

confidence: 99%

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The role of UbiX in Escherichia coli coenzyme Q biosynthesis

Gulmezian¹,

Hyman²,

Marbois³

et al. 2007

Archives of Biochemistry and Biophysics

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The reversible redox chemistry of coenzyme Q serves a crucial function in respiratory electron transport. Biosynthesis of Q in Escherichia coli depends on the ubi genes. However, very little is known about UbiX, an enzyme thought to be involved in the decarboxylation step in Q biosynthesis in E. coli and Salmonella enterica. Here we characterize an E. coli ubiX gene deletion strain, LL1, to further elucidate E. coli ubiX function in Q biosynthesis. LLI produces very low levels of Q, grows slowly on succinate as the sole carbon source, accumulates 4-hydroxy-3-octaprenyl-benzoate, and has reduced UbiG O-methyltransferase activity. Expression of either E. coli ubiX or the Saccharomyces cerevisiae ortholog PAD1, rescues the deficient phenotypes of LL1, identifying PAD1 as an ortholog of ubiX. Our results suggest that both UbiX and UbiD are required for the decarboxylation of 4-hydroxy-3-octaprenyl-benzoate in E. coli coenzyme Q biosynthesis, especially during logarithmic growth.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The role of UbiX in Escherichia coli coenzyme Q biosynthesis

Gulmezian¹,

Hyman²,

Marbois³

et al. 2007

Archives of Biochemistry and Biophysics

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“…The biosynthesis of Q 10 involves three major steps (Olson & Rudney, 1983) Ð synthesis of the ring structure from the essential amino acids tyrosine or phenylalanine, formation of the isoprenoid side chain from acetyl-CoA residues via the mevanolate pathway, and ®nally condensation of these structures by means of the enzyme polyprenyl-transferase, possibly in the Golgi apparatus. An essential step regulating the synthesis seems to be the hydroxymethylglutaryl (HMG)-coenzyme A reductase reaction, common with a step in cholesterol synthesis, but other steps may also be regulated ( Figure 2).…”

Section: Biochemistry and Physiological Effectsmentioning

confidence: 99%

Coenzyme Q10 in health and disease

et al. 1999

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“…2,3 Dolichol, in its phosphorylated form, works as a carrier molecule of oligosaccharides in N-linked protein glycosylation. 4 Ubiquinone functions as an electron acceptor in the mitochondrial respiratory chain, 5 as well as an antioxidant with an important function in the inhibition of lipid peroxidation. 6 Isopentenyladenine is an essential substrate for the modification of some tRNAs.…”

Section: Introductionmentioning

confidence: 99%

Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells

et al. 2001

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Lovastatin is an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the major regulatory enzyme of the mevalonate pathway. We have previously reported that lovastatin induces a significant apoptotic response in human acute myeloid leukemia (AML) cells. To identify the critical biochemical mechanism(s) essential for lovastatin-induced apoptosis, add-back experiments were conducted to determine which downstream product(s) of the mevalonate pathway could suppress this apoptotic response. Apoptosis induced by lovastatin was abrogated by mevalonate (MVA) and geranylgeranyl pyrophosphate (GGPP), and was partially inhibited by farnesyl pyrophosphate (FPP). Other products of the mevalonate pathway including cholesterol, squalene, lanosterol, desmosterol, dolichol, dolichol phosphate, ubiquinone, and isopentenyladenine did not affect lovastatininduced apoptosis in AML cells. Our results suggest that inhibiting geranylgeranylation of target proteins is the predominant mechanism of lovastatin-induced apoptosis in AML cells. In support of this hypothesis, the geranylgeranyl transferase inhibitor (GGTI-298) mimicked the effect of lovastatin, whereas the farnesyl transferase inhibitor (FTI-277) was much less effective at triggering apoptosis in AML cells. Inhibition of geranylgeranylation was monitored and associated with the apoptotic response induced by lovastatin and GGTI-298 in the AML cells. We conclude that blockage of the mevalonate pathway, particularly inhibition of protein geranylgeranylation holds a critical role in the mechanism of lovastatin-induced apoptosis in AML cells. Leukemia (2001Leukemia ( ) 15, 1398Leukemia ( -1407

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Biosynthesis of Ubiquinone

Cited by 159 publications

References 175 publications

The role of UbiX in Escherichia coli coenzyme Q biosynthesis

The role of UbiX in Escherichia coli coenzyme Q biosynthesis

Coenzyme Q10 in health and disease

Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells

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