Biochemistry, cell biology and molecular biology of lipids ofSaccharomyces cerevisiae

Daum, Günther; Lees, N. Douglas; Bard, Martin; Dickson, Robert C.

doi:10.1002/(sici)1097-0061(199812)14:16<1471::aid-yea353>3.0.co;2-y

Cited by 580 publications

(402 citation statements)

References 311 publications

(443 reference statements)

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“…Azoles, such as miconazole, inhibit the action of lanosterol 14α-demethylase which controls an essential intermediate step in the biosynthesis of ergosterol (White et al, 1998, Daum et al, 1998. In contrast, polyenes, such as amphotericin B, bind to ergosterol in the fungal cell membrane creating pores through which cell constituents may escape (Abu Salah, 1996).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, Erg1 encodes squalene epoxidase, which converts squalene to 2,3-oxidosqualene. This is an oxygen-dependent step, and in a cell with reduced respiration there would a consequent reduction in the synthesis of ergosterol (Daum et al 1998), thus leading to the reduced ergosterol content evident in cells exposed to the copper complexes.…”

Section: Discussionmentioning

confidence: 99%

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Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to Amphotericin B and Miconazole

Eshwika

Coyle

Devereux³

et al. 2004

Biometals

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Growth of the pathogenic yeast Candida albicans in sub-MIC (minimum inhibitory concentration) levels of Cu(ClO 4 ) 2 · 6H 2 O and [Cu(phendio) 3 ](ClO 4 ) 2 · 4H 2 O (phendio = 1,10-phenanthroline-5,6-dione) increased the concentration of miconazole and amphotericin B required to achieve the MIC 90 whereas pre-growth in AgClO 4 and [Ag(phendio) 2 ]ClO 4 resulted in a small decrease in the relevant MIC 90 values. The copper complexes reduce the oxygen consumption of C. albicans while the silver complexes increase oxygen consumption. In addition, pregrowth of cells in the copper complexes resulted in a lower ergosterol content while the silver complexes induced an elevation in ergosterol synthesis.The ability of copper and silver complexes to alter the susceptibility of C. albicans to miconazole and amphotericin B may be influenced by their action on respiration, since reduced respiration rates correlate with reduced cellular ergosterol which is the target for amphotericin B. Lower levels of ergosterol have previously been associated with elevated tolerance to this drug. In the case of reduced sensitivity to miconazole, tolerance may be mediated by lower ergosterol synthesis giving rise to fewer toxic side products once biosynthesis is inhibited by miconazole.Abbreviations: phendio = 1,10-phenanthroline-5,6-dione. phen = 1,10-phenanthroline

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to Amphotericin B and Miconazole

Eshwika

Coyle

Devereux³

et al. 2004

Biometals

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“…The reaction is catalyzed by one or more PEMTs that use S-adenosylmethionine (SAM) as a methyl donor (Fig. 2) (91).…”

Section: Alternative Phosphatidylcholine Biosynthesismentioning

confidence: 99%

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

2010

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SummaryThe glycerophospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE) account for greater than 50% of the total phospholipid species in eukaryotic membranes and thus play major roles in the structure and function of those membranes. In most eukaryotic cells, PC and PE are synthesized by an aminoalcoholphosphotransferase reaction, which uses sn-1,2-diradylglycerol and either CDP-choline or CDP-ethanolamine, respectively. This is the last step in a biosynthetic pathway known as the Kennedy pathway, so named after Eugene Kennedy who elucidated it over 50 years ago. This review will cover various aspects of the Kennedy pathway including: each of the biosynthetic steps, the functions and roles of the phospholipid products PC and PE, and how the Kennedy pathway has the potential of being a chemotherapeutic target against cancer and various infectious diseases. IUBMBIUBMB Life, 62(6): [414][415][416][417][418][419][420][421][422][423][424][425][426][427][428] 2010

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“…The ergosterol biosynthetic pathway requires 21 enzymes to produce ergosterol from the initial condensation of acetylCoA (Daum et al, 1998). HMG-CoA reductase (HMG1) is deemed to catalyze the rate-limiting step though overexpression of this enzyme, leading to increased levels of squalene, an upstream intermediate of ergosterol (Polakowski et al, 1998).…”

Section: Ergosterol Requirement For Vacuole Biogenesismentioning

confidence: 99%

Enhanced Membrane Fusion in Sterol-enriched Vacuoles Bypasses the Vrp1p Requirement

Tedrick

Trischuk

Lehner

et al. 2004

MBoC

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Organization of lipids into membrane microdomains is a vital mechanism of protein processing. Here we show that overexpression of ERG6, a gene involved in ergosterol synthesis, elevates sterol levels 1.5-fold on the vacuole membrane and enhances their homotypic fusion. The mechanism of sterol-enhanced fusion is not via more efficient sorting, but instead promotes increased kinetics of fusion subreactions. We initially isolated ERG6 as a suppressor of a vrp1⌬ growth defect selective for vacuole function. VRP1 encodes verprolin, an actin-binding protein that colocalizes to vacuoles. The vrp1⌬ mutant has fragmented vacuoles in vivo and isolated vacuoles do not fuse in vitro, indicative of a Vrp1p requirement for membrane fusion. ERG6 overexpression rescues vrp1⌬ vacuole fusion in a cytosol-dependent manner. Cytosol prepared from the vrp1⌬ strain remains active; therefore, cytosol is not resupplying Vrp1p. Las17p (Vrp1p functional partner) antibodies, which inhibit wild-type vacuole fusion, do not inhibit the fusion of vacuoles from the vrp1⌬-ERG6 overexpression strain. Vacuole-associated actin turnover is decreased in the vrp1⌬ strain, but recovered by ERG6 overexpression linking sterol enrichment to actin remodeling. Therefore, the Vrp1p/Las17p requirement for membrane fusion is bypassed by increased sterols, which promotes actin remodeling as part the membrane fusion mechanism.

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Biochemistry, cell biology and molecular biology of lipids ofSaccharomyces cerevisiae

Cited by 580 publications

References 311 publications

Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to Amphotericin B and Miconazole

Metal complexes of 1,10-phenanthroline-5,6-dione alter the susceptibility of the yeast Candida albicans to Amphotericin B and Miconazole

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

Enhanced Membrane Fusion in Sterol-enriched Vacuoles Bypasses the Vrp1p Requirement

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