Regulation of phosphatidylserine synthase from Saccharomyces cerevisiae by phospholipid precursors

Poole, M. A.; Homann, Michael J.; Bae-Lee, Myong Suk; Carman, George M.

doi:10.1128/jb.168.2.668-672.1986

Cited by 69 publications

(72 citation statements)

References 37 publications

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“…This enzyme is regulated by genetic and biochemical mechanisms that influence the synthesis of phospholipids via the CDP-DAG pathway as well as the synthesis of PI (13,25,123). The expression of CHO1 is repressed by water-soluble phospholipid precursors (67,100,103,104) and in the stationary phase of growth (124,125). The PS synthase enzyme is activated by DGPP, PA, PC, and PI but inhibited by cardiolipin, diacylglycerol, sphingoid bases, inositol, and CTP (20,34,38,40,126).…”

Section: Discussionmentioning

confidence: 99%

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Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Iwanyshyn

Han

Carman

2004

Journal of Biological Chemistry

156

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Zinc is an essential nutrient required for the growth and metabolism of eukaryotic cells. In this work, we examined the effects of zinc depletion on the regulation of phospholipid synthesis in the yeast Saccharomyces cerevisiae. Zinc depletion resulted in a decrease in the activity levels of the CDP-diacylglycerol pathway enzymes phosphatidylserine synthase, phosphatidylserine decarboxylase, phosphatidylethanolamine methyltransferase, and phospholipid methyltransferase. In contrast, the activity of phosphatidylinositol synthase was elevated in response to zinc depletion. The level of Aut7p, a marker for the induction of autophagy, was also elevated in zinc-depleted cells. For the CHO1-encoded phosphatidylserine synthase, the reduction in activity in response to zinc depletion was controlled at the level of transcription. This regulation was mediated through the UAS INO element and by the transcription factors Ino2p, Ino4p, and Opi1p that are responsible for the inositol-mediated regulation of UAS INO -containing genes involved in phospholipid synthesis. Analysis of the cellular composition of the major membrane phospholipids showed that zinc depletion resulted in a 66% decrease in phosphatidylethanolamine and a 29% increase in phosphatidylinositol. A zrt1⌬ zrt2⌬ mutant (defective in the plasma membrane zinc transporters Zrt1p and Zrt2p) grown in the presence of zinc exhibited a phospholipid composition similar to that of wild type cells depleted for zinc. These results indicated that a decrease in the cytoplasmic levels of zinc was responsible for the alterations in phospholipid composition.

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Section: Discussionmentioning

confidence: 99%

“…The expression of the CHO1 gene in wild type S. cerevisiae is repressed by the addition of inositol to the growth medium (100,104). We questioned whether the zinc-mediated regulation of PS synthase was affected by inositol supplementation.…”

Section: Effect Of Inositol On the Zinc-mediated Regulation Of Ps Synmentioning

confidence: 99%

Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Iwanyshyn

Han

Carman

2004

Journal of Biological Chemistry

156

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“…CHO1 expression is regulated by water-soluble phospholipid precursors (e.g. inositol supplementation) (59,90,94,95) and by growth phase (96,97). The activity of PS synthase is modulated by membrane phospholipids (98 -100) and is inhibited by inositol (101) and by CTP (39).…”

Section: Discussionmentioning

confidence: 99%

“…The expression of CHO1 in wild type S. cerevisiae is repressed by the addition of inositol to the growth medium (59,90). To examine whether the cki1⌬ eki1⌬ mutations affected this regulation, ␤-galactosidase activity was measured in wild type and mutant cells grown in the absence and presence of 50 M inositol.…”

Section: Effect Of the Uas Ino Element On The Regulation Of Cho1 Exprmentioning

confidence: 99%

Regulation of Phospholipid Synthesis in the Yeast cki1Δ eki1Δ Mutant Defective in the Kennedy Pathway

Choi

Sreenivas

Han

et al. 2004

Journal of Biological Chemistry

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In the yeast Saccharomyces cerevisiae, the most abundant phospholipid phosphatidylcholine is synthesized by the complementary CDP-diacylglycerol and Kennedy pathways. Using a cki1⌬ eki1⌬ mutant defective in choline kinase and ethanolamine kinase, we examined the consequences of a block in the Kennedy pathway on the regulation of phosphatidylcholine synthesis by the CDP-diacylglycerol pathway. The cki1⌬ eki1⌬ mutant exhibited increases in the synthesis of phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine via the CDP-diacylglycerol pathway. The increase in phospholipid synthesis correlated with increased activity levels of the CDPdiacylglycerol pathway enzymes phosphatidylserine synthase, phosphatidylserine decarboxylase, phosphatidylethanolamine methyltransferase, and phospholipid methyltransferase. However, other enzyme activities, including phosphatidylinositol synthase and phosphatidate phosphatase, were not affected in the cki1⌬ eki1⌬ mutant. For phosphatidylserine synthase, the enzyme catalyzing the committed step in the pathway, activity was regulated by increases in the levels of mRNA and protein. Decay analysis of CHO1 mRNA indicated that a dramatic increase in transcript stability was a major component responsible for the elevated level of phosphatidylserine synthase. These results revealed a novel mechanism that controls phospholipid synthesis in yeast.PC 1 is the most abundant phospholipid in the membranes of eukaryotic cells (1-4). It serves as a structural component of the membrane and as a source of bioactive lipids (e.g. lyso-PC, PA, DAG) (1-5). The importance of PC is underscored by the fact that alterations in its metabolism are linked to apoptosis (6 -9) and oncogenic transformation (10 -12). In the model eukaryote Saccharomyces cerevisiae, PC is synthesized by complementary pathways that are common to those found in mammalian cells 2 ( Fig. 1) (1,4,(13)(14)(15)(16)(17). In the CDP-DAG pathway, PC is synthesized from CDP-DAG via the reactions catalyzed by PS synthase (18 -20), PS decarboxylase (21-23), PE methyltransferase (24, 25), and phospholipid methyltransferase (24,26). In the CDP-choline branch of the Kennedy pathway, PC is synthesized from choline via the reactions catalyzed by choline kinase (27), phosphocholine cytidylyltransferase (28), and choline phosphotransferase (29,30). Analyses of mutations in S. cerevisiae (4, 31, 32), as well as in mammalian cells (33,34) indicate that the physiological role(s) of PC synthesized by the two pathways are different.The contribution of the CDP-DAG and Kennedy pathways for PC synthesis in wild type S. cerevisiae is dependent on the exogenous supply of choline (35). When grown in the presence of choline, yeast primarily synthesizes PC via the Kennedy pathway (35). On the other hand, when cells are grown in the absence of choline, PC is primarily synthesized via the CDP-DAG pathway (35). Yet, even under this growth condition, the Kennedy pathway still contributes to the synthesis of PC (36 -41). The choline required for the Kenne...

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“…synthesis (19). Expression of CDP-DG synthase (21,22,28), PS synthase (2,10,21,27,28,34), and PGP synthase (16) is repressed when wild-type cells are grown in inositol-containing (I+) medium. The level at which PGP synthase is regulated has not been determined, although degradation or inactivation of the enzyme is one likely mechanism (16).…”

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confidence: 99%

Regulation of CDP-diacylglycerol synthesis and utilization by inositol and choline in Schizosaccharomyces pombe

Gaynor

Greenberg

1992

J Bacteriol

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CDP-diacylglycerol (CDP-DG (12,20). In particular, relative amounts of the major anionic phospholipids phosphatidylinositol (PI) and phosphatidylserine (PS) vary in response to the exogenous inositol concentration (12). Thus, when the inositol concentration is low, PI content is decreased while PS content is increased. The precursor to the synthesis of PI and PS is CDP-diacylglycerol (CDP-DG) (Fig. 1). This liponucleotide is an important intermediate in yeast phospholipid synthesis, as it is the direct source of the phosphatidyl moiety in phosphatidylglycerolphosphate (PGP), PI, and PS. PGP is then converted to phosphatidylglycerol and cardiolipin, while PS is converted to phosphatidylethanolamine (PE) and phosphatidylcholine (PC) (7). As CDP-DG is located at a crucial branchpoint in phospholipid synthesis, differential regulation of the enzymes which metabolize it may account for the changes in phospholipid composition observed in response to different physiological conditions.In Saccharomyces cerevisiae, the enzymes which synthesize and utilize CDP-DG are regulated on many levels. Inositol is a key regulator of phospholipid biosynthesis in this lower eucaryote (reviewed in references 7 arid 33). The pathway for conversion of phosphatidate, phosphatidate -)

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Regulation of phosphatidylserine synthase from Saccharomyces cerevisiae by phospholipid precursors

Cited by 69 publications

References 37 publications

Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc

Regulation of Phospholipid Synthesis in the Yeast cki1Δ eki1Δ Mutant Defective in the Kennedy Pathway

Regulation of CDP-diacylglycerol synthesis and utilization by inositol and choline in Schizosaccharomyces pombe

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