Reduction of CDP-diacylglycerol Synthase Activity Results in the Excretion of Inositol by Saccharomyces cerevisiae

Shen, Haifa; Dowhan, William

doi:10.1074/jbc.271.46.29043

Cited by 27 publications

(16 citation statements)

References 46 publications

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“…Thus, the regulation of its expression provides a mechanism for controlling the synthesis of CDP-DAG from PA and the CDP-DAGdependent synthesis of phospholipids. This notion is supported by genetic evidence that a cds1 mutant defective in CDP-DAG synthase activity exhibits an elevated PA content and the derepression of UAS INO -containing genes (50,51). The increased DAG levels caused by the CDP-DAG-mediated regulation of PA phosphatase and DAG kinase activities would be channeled to phospholipids via the Kennedy pathway or to the storage lipid TAG.…”

Section: Roles Of Pa Phosphatase and Dag Kinase Insupporting

confidence: 56%

Regulation of phospholipid synthesis in yeast

Carman

Han

2009

Journal of Lipid Research

102

109

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Phospholipid synthesis in the yeast Saccharomyces cerevisiae is a complex process that involves regulation by both genetic and biochemical mechanisms. The activity levels of phospholipid synthesis enzymes are controlled by gene expression (e.g., transcription) and by factors (lipids, water-soluble phospholipid precursors and products, and covalent modification of phosphorylation) that modulate catalysis. Phosphatidic acid, whose levels are controlled by the biochemical regulation of key phospholipid synthesis enzymes, plays a central role in the regulation of phospholipid synthesis gene expression.-Carman, G. M., and G-S. Han. Regulation of phospholipid synthesis in yeast. J. Lipid Res. 2009. 50: S69-S73.

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Section: Roles Of Pa Phosphatase and Dag Kinase Insupporting

confidence: 56%

Regulation of phospholipid synthesis in yeast

Carman

Han

2009

Journal of Lipid Research

102

109

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“…However, there was no increase in the mutant strain relative to the wild type strain until CDP-DAG synthase activity was well below the wild type level (Fig. 3), correlating with our previous observation that the cds1 mutant excreted inositol into the growth medium only when cellular CDP-DAG synthase activity was low (19,21). The PIS1 mRNA level remained the same (Fig.…”

Section: Fig 2 Cdp-dag Ps and Pi Synthase Activities As A Functiosupporting

confidence: 73%

“…Enzyme Assays-Activities of CDP-DAG synthase, PI synthase, and PS synthase were determined as described previously (21). Briefly, the total cell membrane fraction was resuspended in 20 mM Tris-maleate, pH 7.0.…”

Section: Methodsmentioning

confidence: 99%

“…Reduced synthase levels also resulted in inositol excretion. By characterizing the cdg1 mutant (20), we found a point mutation within the CDS1 gene that results in the cdg1 phenotype of pleiotropic deficiencies in phospholipid biosynthesis, including a reduced level of CDP-DAG synthase activity, an elevated phosphatidic acid content, a constitutive elevated level of inositol 1-phosphate synthase activity, and an elevated PS synthase activity (21). All of these results are suggestive of alteration of expression of the INO1 and CHO1/PSS genes at reduced cellular CDP-DAG synthase levels.…”

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confidence: 99%

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Regulation of Phospholipid Biosynthetic Enzymes by the Level of CDP-Diacylglycerol Synthase Activity

Shen¹,

Dowhan²

1997

Journal of Biological Chemistry

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Amine-containing phospholipid synthesis in Saccharomyces cerevisiae starts with the conversion of CDPdiacylglycerol (CDP-DAG) and serine to phosphatidylserine (PS), whereas phosphatidylinositol (PI) is formed from CDP-DAG and inositol (derived from inositol 1-phosphate). In this study the regulation of PS synthase (encoded by CHO1/PSS), PI synthase (encoded by PIS1), and inositol 1-phosphate synthase (encoded by INO1) activities by the in vivo level of CDP-DAG synthase activity (encoded by CDS1) is described. Reduction in the level of CDP-DAG synthase activity from 10-fold over wild type levels to 10% of wild type levels results in a 7-fold increase in PS synthase activity, which follows a similar change in the CHO1/PSS mRNA level. INO1 mRNA also increases but only after CDP-DAG synthase activity falls below the wild type level. PI synthase activity follows the decrease of the CDP-DAG synthase activity, but there is no parallel change in the level of PIS1 mRNA. These changes in CHO1/PSS and INO1 mRNA levels are mediated by a mechanism not dependent on changes in the expression of the INO2-OPI1 regulatory genes. CDS1 expression is repressed in concert with INO2 expression in response to inositol.The major phospholipids in yeast, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine (PS), 1 and phosphatidylinositol (PI), are synthesized by two branches of the phospholipid biosynthetic pathway that diverge from the common liponucleotide precursor CDP-diacylglycerol (CDP-DAG) (1-3). Synthesis of amine-containing lipids starts with the conversion of CDP-DAG and serine to PS, which is sequentially converted to phosphatidylethanolamine and phosphatidylcholine. PI is synthesized from CDP-DAG and inositol, which can be synthesized de novo from glucose 6-phosphate catalyzed by inositol 1-phosphate synthase, the product of the INO1 gene (4). PS synthase encoded by the CHO1/PSS gene (5, 6) and PI synthase encoded by the PIS1 gene (7), respectively, catalyze the above two CDP-DAG-dependent reactions. The cellular activities of PS synthase and PI synthase, together with the availability of inositol, have been considered to be the major determinants in the partitioning of CDP-DAG between these two branches of the pathway and consequently determine the final membrane phospholipid composition (8). Therefore, it is not surprising that these enzymes are regulated at multiple levels to coordinate phospholipid biosynthesis.Studies of the regulation of phospholipid biosynthesis by inositol demonstrate that the INO1 and CHO1/PSS genes are derepressed in wild type cells grown in medium lacking inositol and choline (or ethanolamine), and repressed when these precursors of phospholipid biosynthesis are present (9, 10); choline and ethanolamine are precursors in the DAG-dependent pathway leading to phosphatidylcholine and phosphatidylethanolamine biosynthesis (1, 3). The regulation of INO1 and CHO1/ PSS gene expression by inositol and choline has been shown to occur at the level of mRNA abundance (11,12) and is mediated by the...

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“…cds1) is lethal (58). However, partial (59) or conditional (60) cds1 alleles derepress INO1 and excrete inositol (60). The inositol excretion phenotype of the cds1 mutants cannot be overcome by supplementation with a Kennedy pathway precursor, nor will inositol mediate the repression of other UAS INO -containing genes in these strains (31,32,59).…”

Section: Genetic Clues Implicating Pa As the Signaling Molecule That mentioning

confidence: 99%

Phosphatidic Acid Plays a Central Role in the Transcriptional Regulation of Glycerophospholipid Synthesis in Saccharomyces cerevisiae

Carman

Henry

2007

Journal of Biological Chemistry

195

284

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Reduction of CDP-diacylglycerol Synthase Activity Results in the Excretion of Inositol by Saccharomyces cerevisiae

Cited by 27 publications

References 46 publications

Regulation of phospholipid synthesis in yeast

Regulation of phospholipid synthesis in yeast

Regulation of Phospholipid Biosynthetic Enzymes by the Level of CDP-Diacylglycerol Synthase Activity

Phosphatidic Acid Plays a Central Role in the Transcriptional Regulation of Glycerophospholipid Synthesis in Saccharomyces cerevisiae

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