Physiological and genetic analysis of the carbon regulation of the NAD-dependent glutamate dehydrogenase of Saccharomyces cerevisiae.

Coschigano, Peter W.; Miller, Steven M.; Magasanik, Boris

doi:10.1128/mcb.11.9.4455

Cited by 43 publications

(66 citation statements)

References 56 publications

(32 reference statements)

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“…It has been recognized that the expression of the NAD-GDH catabolic enzyme is induced in the presence of ethanol (43). However, the physiological significance of this observation has remained obscure, since gdh2⌬ mutants show no evident phenotype in ethanol-grown cultures.…”

Section: Discussionmentioning

confidence: 99%

“…These results are in agreement with the fact that Gdh1p enzyme has a higher rate of ␣-ketoglutarate utilization than the heteromeric enzyme that exists in ethanol-grown cells. Moreover, NAD-GDH specific activity was induced 3-fold in ethanol-grown cells lacking the Gdh3p enzyme (Table III), indicating that under this condition glutamate accumulated, resulting in induced GDH2 expression (43).…”

Section: Nadp-gdh Purification From Mutant and Wild-typementioning

confidence: 98%

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NADP-Glutamate Dehydrogenase Isoenzymes of Saccharomyces cerevisiae

DeLuna¹,

Avendaño

Riego

et al. 2001

Journal of Biological Chemistry

140

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In the yeast Saccharomyces cerevisiae, two NADP؉ -dependent glutamate dehydrogenases (NADP-GDHs) encoded by GDH1 and GDH3 catalyze the synthesis of glutamate from ammonium and ␣-ketoglutarate. The GDH2-encoded NAD ؉ -dependent glutamate dehydrogenase degrades glutamate producing ammonium and ␣-ketoglutarate. Until very recently, it was considered that only one biosynthetic NADP-GDH was present in S. cerevisiae. This fact hindered understanding the physiological role of each isoenzyme and the mechanisms involved in ␣-ketoglutarate channeling for glutamate biosynthesis. In this study, we purified and characterized the GDH1-and GDH3-encoded NADP-GDHs; they showed different allosteric properties and rates of ␣-ketoglutarate utilization. Analysis of the relative levels of these proteins revealed that the expression of GDH1 and GDH3 is differentially regulated and depends on the nature of the carbon source. Moreover, the physiological study of mutants lacking or overexpressing GDH1 or GDH3 suggested that these genes play nonredundant physiological roles. Our results indicate that the coordinated regulation of GDH1-, GDH3-, and GDH2-encoded enzymes results in glutamate biosynthesis and balanced utilization of ␣-ketoglutarate under fermentative and respiratory conditions. The possible relevance of the duplicated NADP-GDH pathway in the adaptation to facultative metabolism is discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Nadp-gdh Purification From Mutant and Wild-typementioning

confidence: 98%

NADP-Glutamate Dehydrogenase Isoenzymes of Saccharomyces cerevisiae

DeLuna¹,

Avendaño

Riego

et al. 2001

Journal of Biological Chemistry

140

View full text Add to dashboard Cite

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“…The synthesis of this enzyme is also repressed by glucose (Eraso and Gancedo, 1984) and this repression appears to depend on the presence of a repressing nitrogen source like glutamine (Coschigano et al, 1991). The cyc8 mutation allows a partial derepression of GDH2 in the presence of glucose but neither HXK2 nor HAP3 or HAP4 appear to be involved in its regulation; other regulatory mutants which affect other systems subject to catabolite repression have not been tested.…”

Section: Nad-dependent Glutamate Dehydrogenasementioning

confidence: 99%

Carbon catabolite repression in yeast

Gancedo

1992

European Journal of Biochemistry

410

247

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Control of gene expression is a basic regulatory mechanism of living organisms. In microorganisms, glucose or other rapidly metabolizable carbon sources repress the expression of genes that code for enzymes related to the metabolism of other carbon sources. This phenomenon, known as catabolite repression, allows microorganisms to cope effectively with changes in the carbon sources present in their environment. In the case of Escherichiu coli, a model to explain at the molecular level the mechanism of catabolite repression has been worked out (Ullmann, 1985;Saier, 1989), although some of its elements remain unidentified.Yeasts are also subject to carbon catabolite repression but the underlying mechanism(s) is less understood than it is in E. coli and we do not yet know how glucose exerts its repressive effect. In the present article I will review information gathered in the last few years on a variety of catabolite-repressible systems, try to integrate it and to elaborate a scheme for carbon catabolite repression consistent with the results obtained. Although this review will be centered around Sacchuromyces cerevisiue, reference to other yeast species will be made when information is available.The degree of repression caused by glucose depends strongly on the enzyme affected and the strain used. As shown in Table 1, it can vary from about 800-fold for invertase to less than 10-fold for aconitase, cytochrome c oxidase or isocitrate dehydrogenase. In most cases, the decrease in enzyme levels caused by glucose is paralleled by a decrease in the concentration of the corresponding mRNA. This could be due to an effect of glucose either on the rate of transcription, or on the stability of the corresponding mRNA or on both.Direct measurements of transcription rates have been performed in only a few cases. For the genes CYCI, encoding iso-1 cytochrome c, and MAL6S, encoding maltase, it was found that derepressed cells synthesized the corresponding mRNAs 6 times and 15 times faster, respectively, than repressed cells (Zitomer et al., 1979;Federoff et al., 1983a). It should be noted that, in the case of maltase, an induction by maltose is superimposed on the process of catabolite repression, but even in the presence of maltose, the addition of glucose to a yeast culture causes an approximately I5-fold decrease in the rate of transcription of the MAL6S gene in Correspondence to J. M. Gancedo,

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“…In metabolic terms, when glucose is limiting or substituted, oxidative metabolism is preferred over fermentative metabolism and there is an increase in respiration and electron transport (10). Under these conditions amino acids, through trans-and deamination, may be used to replenish the increased activity of the tricarboxylic acid cycle (11) leading to an increased requirement in their uptake from the medium. One way of fulfilling this requirement would be to increase the import of amino acids via the various yeast amino acid permeases (12).…”

mentioning

confidence: 99%

Carbon Catabolite Repression Regulates Amino Acid Permeases in Saccharomyces cerevisiae via the TOR Signaling Pathway

Peter

Düring

Ahmed

2006

Journal of Biological Chemistry

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We have identified carbon catabolite repression (CCR) as a regulator of amino acid permeases in Saccharomyces cerevisiae, elucidated the permeases regulated by CCR, and identified the mechanisms involved in amino acid permease regulation by CCR. Transport of L-arginine and L-leucine was increased by ϳ10 -25-fold in yeast grown in carbon sources alternate to glucose, indicating regulation by CCR. In wild type yeast the uptake (pmol/10 6 cells/ h), in glucose versus galactose medium, of L-[ 14 C]arginine was (0.24 ؎ 0.04 versus 6.11 ؎ 0.42) and L-[ 14 C]leucine was (0.30 ؎ 0.02 versus 3.60 ؎ 0.50). The increase in amino acid uptake was maintained when galactose was replaced with glycerol. Deletion of gap1⌬ and agp1⌬ from the wild type strain did not alter CCR induced increase in L-leucine uptake; however, deletion of further amino acid permeases reduced the increase in L-leucine uptake in the following manner: 36% (gnp1⌬), 62% (bap2⌬), 83% (⌬(bap2-tat1)). Direct immunofluorescence showed large increases in the expression of Gnp1 and Bap2 proteins when grown in galactose compared with glucose medium. By extending the functional genomic approach to include major nutritional transducers of CCR in yeast, we concluded that SNF/MIG, GCN, or PSK pathways were not involved in the regulation of amino acid permeases by CCR. Strikingly, the deletion of TOR1, which regulates cellular response to changes in nitrogen availability, from the wild type strain abolished the CCR-induced amino acid uptake. Our results provide novel insights into the regulation of yeast amino acid permeases and signaling mechanisms involved in this regulation.The preferred mode of metabolism in Saccharomyces cerevisiae is fermentative, and the preferred carbon source is glucose; other carbohydrates such as galactose or maltose and non-fermentable carbon sources such as ethanol and glycerol could also be utilized by yeast (1). Substitution, reduction, or removal of glucose from the laboratory growth medium, however, is known to have important physiological and genomic consequences in yeast (1-3).The presence of a high concentration of glucose in the growth medium represses transcription of multiple genes including those involved in alternative carbohydrate and mitochondrial metabolism (1, 3). This phenomenon is known as carbon catabolite repression (CCR, 2 gene regulation processes that are initiated when glucose is removed as a source of carbon in the growth medium; reviewed by Refs. 1 and 4). Two nutrient signaling transducers, namely SNF1 and GCN2, are known to play a major role in global gene regulation by CCR. SNF1 is a yeast homologue of the AMP-activated protein kinase that regulates CCR through the MIG1 protein (5). During the conditions of low glucose and starvation of amino acids, GCN2 kinase is also involved in nutrient signaling in yeast (4). TOR is another important nutritional transducer that regulates various cellular processes including protein synthesis and autophagy (6) but in response to the availability of nitrogen. The TOR pathway ...

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Physiological and genetic analysis of the carbon regulation of the NAD-dependent glutamate dehydrogenase of Saccharomyces cerevisiae.

Cited by 43 publications

References 56 publications

NADP-Glutamate Dehydrogenase Isoenzymes of Saccharomyces cerevisiae

NADP-Glutamate Dehydrogenase Isoenzymes of Saccharomyces cerevisiae

Carbon catabolite repression in yeast

Carbon Catabolite Repression Regulates Amino Acid Permeases in Saccharomyces cerevisiae via the TOR Signaling Pathway

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