Regulation of the biosynthesis of cytochrome P-450 in brewer's yeast role of cyclic AMP

Wiseman, Alan; Lim, T.-K.; Woods, Leonard F. J.

doi:10.1016/0304-4165(78)90335-5

Cited by 40 publications

(6 citation statements)

References 43 publications

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“…Moreover, yeast cytochromes produced as part of the biosynthesis pathway for ergosterol, which is an important component of yeast membranes, have been shown to be able to metabolize exogenous chemicals as a side reaction (Alexander et al, 1974; Aoyama and Yoshida, 1978). Specifically, these enzymes are capable of oxidizing compounds to the toxic quinones and epoxides, which are products of BAP metabolism (Wiseman et al, 1978). In addition, these enzymes have also been shown to metabolize pro-carcinogens to their carcinogenic form (Callen et al, 1980).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Functional and Stress Response Profiling Reveals Toxic Mechanism and Genes Required for Tolerance to Benzo[a]pyrene in S. cerevisiae

O’Connor¹,

Lan²,

North³

et al. 2013

Front. Gene.

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Benzo[a]pyrene (BaP) is a ubiquitous, potent, and complete carcinogen resulting from incomplete organic combustion. BaP can form DNA adducts but other mechanisms may play a role in toxicity. We used a functional toxicology approach in S. cerevisiae to assess the genetic requirements for cellular resistance to BaP. In addition, we examined translational activities of key genes involved in various stress response pathways. We identified multiple genes and processes involved in modulating BaP toxicity in yeast which support DNA damage as a primary mechanism of toxicity, but also identify other potential toxicity pathways. Gene ontology enrichment analysis indicated that DNA damage and repair as well as redox homeostasis and oxidative stress are key processes in cellular response to BaP suggesting a similar mode of action of BaP in yeast and mammals. Interestingly, toxicant export is also implicated as a potential novel modulator of cellular susceptibility. In particular, we identified several transporters with human orthologs (solute carrier family 22) which may play a role in mammalian systems.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Functional and Stress Response Profiling Reveals Toxic Mechanism and Genes Required for Tolerance to Benzo[a]pyrene in S. cerevisiae

O’Connor¹,

Lan²,

North³

et al. 2013

Front. Gene.

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“…Wiseman and Woods (51) showed that the presence of cAMP repressed the de novo production of P-450 in protoplasts of S. cerevisiae 240 (later shown to have benzo[a]pyrene hydroxylase activity [22]). In contrast, cAMP is the second messenger of mammalian P-450 enzymes which are induced by pituitary hormones, and addition of cAMP or cAMP analogs to cells often stimulates P-450 production (57).…”

Section: Resultsmentioning

confidence: 99%

“…King et al (22) have shown that a benzo[a]pyrene hydroxylase can be induced in a particular strain of S. cerevisiae. Previous studies with this strain demonstrated a negative correlation between cellular cyclic AMP (cAMP) content and P-450 concentration (51), which is unlike the hormone-inducible mammalian P-450s involved in mammalian steroidogenesis in which cAMP is thought to be the second messenger (47). * Corresponding author.…”

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confidence: 99%

Induction and substrate specificity of the lanosterol 14 alpha-demethylase from Saccharomyces cerevisiae Y222

Wright

Honek

1991

J Bacteriol

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The potential inducibility of the lanosterol 14at-demethylase (P-45014DM) from Saccharomyces cerevisiae Y222 by xenobiotics was investigated. This enzyme and NADPH-cytochrome P-450 reductase were unaffected by a number of compounds known to induce mammalian and some yeast cytochrome P-450 monooxygenases. Furthermore, dibutyryl cyclic AMP did not affect P-45014DM or P-450 reductase levels, while growth at 37°C resulted in a slight decrease. P-45014DM was found to be specific for lanosterol and did not metabolize a number of P-450 substrates including benzo[alpyrene.The lanosterol 14a-demethylase (P-45014DM) in yeasts and fungi is the target for the clinically and agriculturally important imidazole and triazole antifungal agents (5,43,55). Inhibition of this membrane-bound cytochrome P-450 monooxygenase (P-450) results in decreased biosynthesis of the major fungal sterol ergosterol and accumulation of C-14-methylated sterol precursors. Ergosterol depletion results in altered membrane permeability and decreased activity of membrane enzymes such as chitin synthetase (42), which may contribute to inhibition of fungal growth. P-45014DM from the yeasts Saccharomyces cerevisiae and Candida albicans has been purified (15, 56) and cloned (18,25).Many mammalian P-450s can be induced by a variety of compounds. In particular, these chemicals induce a specific enzyme, or group of enzymes, which catalyze distinct reactions (47, 53). There are several different classes of compounds which are known to induce mammalian P-450s; these include the phenobarbital class of compounds (12), polyaromatic hydrocarbons (e.g., 3-methylcholanthrene) (28), steroids (e.g., dexamethasone) (35), pituitary hormones (44), and ethanol (37), among others. P-450s in S. cerevisiae have been shown to catalyze a number of reactions, including lanosterol demethylation (2), A22-sterol desaturation (13), hydroxylation of benzo[a]pyrene (52), deethylation of 7-ethoxycoumarin (8), and activation of promutagens such as dimethylnitrosamine (6). Little is known about the induction of P-450 in yeasts. Ishidate and coworkers (17) We have previously noted a relationship between iron and P-450 content in S. cerevisiae Y222 (54).While it seems probable that the various reactions catalyzed by P-450s are performed by distinct enzymes, only one P-450 locus has yet been identified in S. cerevisiae (18). Because of the small quantities of P-450 in yeast and fungi compared with those in mammalian sources, extensive studies on these enzymes are hampered by the availability of P-450. In this study we have investigated the induction of P-45014DM in S. cerevisiae Y222. It is shown that this enzyme is the only P-450 produced by this organism and that it does not metabolize a number of mammalian P-450 substrates. MATERIALS AND METHODSMaterials. trans-1,4-Bis(2-chlorobenzylaminomethylcyclohexane dihydrochloride) (AY-9944) was a gift from WyethAyerst Research (Princeton, N.J.). Benzo[a]pyrene, 3-methylcholanthrene, dilaurylphosphatidylcholine, Tergitol 15-S-12, and lanosterol w...

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“…Spectra of reduced, oxidized, and reduced and CO-bubbled pellets were taken at room temperature over 650 to 350 and 500 to 380 nm, with PTFE powder as a blank. Cytochromes were determined from dithionite-reduced minus H202-oxidized difference spectra, whereas CO-binding pigments were estimated from the CO-plus-dithionite-reduced versus dithionite-reduced difference spectra (35).…”

Section: Methodsmentioning

confidence: 99%

Analysis of Fungal Pellets by UV-Visible Spectrum Diffuse Reflectance Spectroscopy

Leštan

Podgornik

Perdih

1993

Appl Environ Microbiol

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The application of the UV-visible spectrum diffuse reflectance spectroscopy for the determination of intracellular pH in vivo, for determination of cytochrome content, and for the noninvasive in vivo detection of the redox state of fungal mitochondrial cytochromes in filamentous fungi is introduced. The time course of the intracellular pH values, mitochondrial cytochromes, and CO-binding pigments content and the correlations between the actual redox state of cytochrome aa3 and saturation of growth medium with oxygen in pellets of the basidiomycete Phanerochaete chrysosporium were determined. As the test microorganism, the yeast Saccharomyces cerevisiae was used. UV-visible spectrum diffuse reflectance spectroscopy proved to be a promising method for the quick and simple analysis of light-impermeable biological structures for which the classical transmittance spectrophotometric methods are difficult to implement.

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Regulation of the biosynthesis of cytochrome P-450 in brewer's yeast role of cyclic AMP

Cited by 40 publications

References 43 publications

Genome-Wide Functional and Stress Response Profiling Reveals Toxic Mechanism and Genes Required for Tolerance to Benzo[a]pyrene in S. cerevisiae

Genome-Wide Functional and Stress Response Profiling Reveals Toxic Mechanism and Genes Required for Tolerance to Benzo[a]pyrene in S. cerevisiae

Induction and substrate specificity of the lanosterol 14 alpha-demethylase from Saccharomyces cerevisiae Y222

Analysis of Fungal Pellets by UV-Visible Spectrum Diffuse Reflectance Spectroscopy

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