Reverse Methionine Biosynthesis fromS-Adenosylmethionine in Eukaryotic Cells

Thomas, Dominique; Becker, Aline Paixão; Surdin-Kerjan, Yolande

doi:10.1074/jbc.m005967200

Cited by 47 publications

(61 citation statements)

References 32 publications

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“…The isa mutants are not impaired in desthiobiotin uptake, as was evident from the fact that their biotin-dependent enzymes were desthiobiotinylated in the absence of biotin. In addition, these cells must be capable of producing SAM, as this is an essential metabolite (58). Sulfur is most likely derived from cysteine and transferred via one of the two Fe/S clusters of biotin synthase (59).…”

Section: Discussionmentioning

confidence: 99%

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

et al. 2007

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The yeast Saccharomyces cerevisiae is able to use some biotin precursors for biotin biosynthesis. Insertion of a sulfur atom into desthiobiotin, the final step in the biosynthetic pathway, is catalyzed by biotin synthase (Bio2). This mitochondrial protein contains two iron-sulfur (Fe/S) clusters that catalyze the reaction and are thought to act as a sulfur donor. To identify new components of biotin metabolism, we performed a genetic screen and found that Isa2, a mitochondrial protein involved in the formation of Fe/S proteins, is necessary for the conversion of desthiobiotin to biotin. Depletion of Isa2 or the related Isa1, however, did not prevent the de novo synthesis of any of the two Fe/S centers of Bio2. In contrast, Fe/S cluster assembly on Bio2 strongly depended on the Isu1 and Isu2 proteins. Both isa mutants contained low levels of Bio2. This phenotype was also found in other mutants impaired in mitochondrial Fe/S protein assembly and in wild-type cells grown under iron limitation. Low Bio2 levels, however, did not cause the inability of isa mutants to utilize desthiobiotin, since this defect was not cured by overexpression of BIO2. Thus, the Isa proteins are crucial for the in vivo function of biotin synthase but not for the de novo synthesis of its Fe/S clusters. Our data demonstrate that the Isa proteins are essential for the catalytic activity of Bio2 in vivo.

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Section: Discussionmentioning

confidence: 99%

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

et al. 2007

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“…Six of them are among the eight target genes of the Cbf1-Met4-Met28 transcription complex mediating the repression of transcription in response to methionine (124), and the two others are also known to be repressed by methionine (52,123). The two remaining Cbf1-Met4-Met28 target genes (MET10 and MET2) are also expressed to a lower level on methionine medium in our study but are not among the 506 genes displaying significant variation of expression on one or more tested nitrogen sources from that on urea.…”

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confidence: 99%

Effect of 21 Different Nitrogen Sources on Global Gene Expression in the YeastSaccharomyces cerevisiae

Godard

Urrestarazu

Vissers

et al. 2007

Molecular and Cellular Biology

217

270

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We compared the transcriptomes of Saccharomyces cerevisiae cells growing under steady-state conditions on 21 unique sources of nitrogen. We found 506 genes differentially regulated by nitrogen and estimated the activation degrees of all identified nitrogen-responding transcriptional controls according to the nitrogen source. One main group of nitrogenous compounds supports fast growth and a highly active nitrogen catabolite repression (NCR) control. Catabolism of these compounds typically yields carbon derivatives directly assimilable by a cell's metabolism. Another group of nitrogen compounds supports slower growth, is associated with excretion by cells of nonmetabolizable carbon compounds such as fusel oils, and is characterized by activation of the general control of amino acid biosynthesis (GAAC). Furthermore, NCR and GAAC appear interlinked, since expression of the GCN4 gene encoding the transcription factor that mediates GAAC is subject to NCR. We also observed that several transcriptional-regulation systems are active under a wider range of nitrogen supply conditions than anticipated. Other transcriptional-regulation systems acting on genes not involved in nitrogen metabolism, e.g., the pleiotropic-drug resistance and the unfolded-protein response systems, also respond to nitrogen. We have completed the lists of target genes of several nitrogen-sensitive regulons and have used sequence comparison tools to propose functions for about 20 orphan genes. Similar studies conducted for other nutrients should provide a more complete view of alternative metabolic pathways in yeast and contribute to the attribution of functions to many other orphan genes.

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“…Previous studies have shown that there are at least two homocysteine methyltransferase enzymes present in Saccharomyces cerevisiae (28,29). These are encoded by the SAM4 and MHT1 genes and utilize AdoMet and S-methylmethionine, respectively, as methyl donors (29). It is not clear whether either of these enzymes was responsible for the utilization of (R,S)-AdoMet seen initially (23).…”

mentioning

confidence: 80%

“…In this work, homocysteine methyltransferase activity was observed at twice the rate when an S,S/R,S mixture of AdoMet was used compared with that seen with the S,S form at an equal total concentration (23). Previous studies have shown that there are at least two homocysteine methyltransferase enzymes present in Saccharomyces cerevisiae (28,29). These are encoded by the SAM4 and MHT1 genes and utilize AdoMet and S-methylmethionine, respectively, as methyl donors (29).…”

mentioning

confidence: 97%

Recognition of Age-damaged (R,S)-Adenosyl-L-methionine by Two Methyltransferases in the Yeast Saccharomyces cerevisiae

Vinci¹,

Clarke²

2007

Journal of Biological Chemistry

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The biological methyl donor S-adenosylmethionine (AdoMet) can exist in two diastereoisomeric states with respect to its sulfonium ion. The S configuration, (S,S)-AdoMet, is the only form that is produced enzymatically as well as the only form used in almost all biological methylation reactions. Under physiological conditions, however, the sulfonium ion can spontaneously racemize to the R form, producing (R,S)-AdoMet. As of yet, (R,S)-AdoMet has no known physiological function and may inhibit cellular reactions. In this study, we found two Saccharomyces cerevisiae enzymes that are capable of recognizing (R,S)-AdoMet and using it to methylate homocysteine to form methionine. These enzymes are the products of the SAM4 and MHT1 genes, identified previously as homocysteine methyltransferases dependent upon AdoMet and S-methylmethionine, respectively. We found here that Sam4 recognizes both (S,S)-and (R,S)-AdoMet, but that its activity is much higher with the R,S form. Mht1 reacts with only the R,S form of AdoMet, whereas no activity is seen with the S,S form. R,S-Specific homocysteine methyltransferase activity is also shown here to occur in extracts of Arabidopsis thaliana, Drosophila melanogaster, and Caenorhabditis elegans, but has not been detected in several tissue extracts of Mus musculus. Such activity may function to prevent the accumulation of (R,S)-AdoMet in these organisms.The aging process, as well as several human diseases, has been linked to the accumulation of spontaneously damaged biomolecules. Cells have evolved several ways of dealing with these altered molecules, including degradation, excretion, and repair pathways (1-6). The balance between the formation of age-altered molecules and the pathways that limit their cellular accumulation has been described as a battle between chemistry and biochemistry, where chemistry ultimately wins (2).Although enzymes that recognize damaged DNA (3) and proteins (1, 2, 5) have been well characterized, this is not yet the case for spontaneously altered small molecules. Of the large number of metabolites that are produced and used by biological systems, many are unstable, degrading into forms that may have reduced function or that may be toxic. One pathway of small molecule degradation and cellular recognition has been described recently. Here, trans-aconitate formed spontaneously from the citric acid cycle intermediate cis-aconitate results in the inhibition of at least two steps in the cycle (7, 8). trans-Aconitate is then recognized by a specific yeast methyltransferase; the methyl ester formed has reduced inhibitory properties (9).One of the crucial small molecule metabolites in all organisms is S-adenosyl-L-methionine (AdoMet) 2 (10 -12). Second to ATP, it is probably the most widely used cofactor in nature (12, 13). Not only does it serve as the primary methyl donor, but it also functions as an amino, adenosyl, and ribosyl donor (11). It also plays a role in the formation of adenosyl radicals (14) and as a precursor of polyamines (15). AdoMet has been shown to...

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Reverse Methionine Biosynthesis fromS-Adenosylmethionine in Eukaryotic Cells

Cited by 47 publications

References 32 publications

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

Effect of 21 Different Nitrogen Sources on Global Gene Expression in the YeastSaccharomyces cerevisiae

Recognition of Age-damaged (R,S)-Adenosyl-L-methionine by Two Methyltransferases in the Yeast Saccharomyces cerevisiae

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