Phospholipid biosynthesis in the yeast Saccharomyces cerevisiae and interrelationship with other metabolic processes

Carman, George M.; Henry, Susan A.

doi:10.1016/s0163-7827(99)00010-7

Cited by 306 publications

(484 citation statements)

References 266 publications

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“…In contrast, changes in CK activity can influence the rate of PC synthesis (48)(49)(50). CK overexpression has been extensively related to cell proliferation, with phosphocholine acting as a second messenger required for DNA synthesis induced by growth factors.…”

Section: The Choline and Ethanolamine Kinasesmentioning

confidence: 99%

“…CK overexpression has been extensively related to cell proliferation, with phosphocholine acting as a second messenger required for DNA synthesis induced by growth factors. Increased levels of CK and phosphocholine can also be observed in several mammalian tumors (see later) and are believed to play an essential role in cell transformation (48)(49)(50). The differential expression of various isoforms of CK in different tissues may represent an alternative way of regulating the flux through the CDP-choline pathway.…”

Section: The Choline and Ethanolamine Kinasesmentioning

confidence: 99%

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The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

2010

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SummaryThe glycerophospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE) account for greater than 50% of the total phospholipid species in eukaryotic membranes and thus play major roles in the structure and function of those membranes. In most eukaryotic cells, PC and PE are synthesized by an aminoalcoholphosphotransferase reaction, which uses sn-1,2-diradylglycerol and either CDP-choline or CDP-ethanolamine, respectively. This is the last step in a biosynthetic pathway known as the Kennedy pathway, so named after Eugene Kennedy who elucidated it over 50 years ago. This review will cover various aspects of the Kennedy pathway including: each of the biosynthetic steps, the functions and roles of the phospholipid products PC and PE, and how the Kennedy pathway has the potential of being a chemotherapeutic target against cancer and various infectious diseases. IUBMBIUBMB Life, 62(6): [414][415][416][417][418][419][420][421][422][423][424][425][426][427][428] 2010

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Section: The Choline and Ethanolamine Kinasesmentioning

confidence: 99%

Section: The Choline and Ethanolamine Kinasesmentioning

confidence: 99%

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

2010

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“…The inositol response in yeast is known to be mediated by the Ino2p-Ino4p bHLH dimer, which regulates the phospholipid biosynthetic genes (Carman and Henry, 1999;Greenberg and Lopes, 1996;Henry and Patton-Vogt, 1998;Jesch et al, 2005;Robinson and Lopes, 2000a;Santiago and Mamoun, 2003). Therefore, the current study suggests that CIT2 expression is coordinated with phospholipid biosynthesis.…”

Section: Discussionmentioning

confidence: 65%

Multiple bHLH proteins regulate CIT2 expression in Saccharomyces cerevisiae

Chen¹,

Lopes²

2010

Yeast

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The basic helix-loop-helix (bHLH) proteins comprise a eukaryotic transcription factor family involved in multiple biological processes. They have the ability to form multiple dimer combinations and most of them also bind a 6 bp site (E-box) with limited specificity. These properties make them ideal for combinatorial regulation of gene expression. The Saccharomyces cerevisiae CIT2 gene, which encodes citrate synthase, was previously known to be induced by the bHLH proteins Rtg1p and Rtg3p in response to mitochondrial damage. Rtg1p-Rtg3p dimers bind two R-boxes (modified E-boxes) in the CIT2 promoter. The current study tested the ability of all nine S. cerevisiae bHLH proteins to regulate the CIT2 gene. The results showed that expression of CIT2-lacZ reporter was induced in a ρ 0 strain by the presence of inositol via the Ino2p and Ino4p bHLH proteins, which are known regulators of phospholipid synthesis. Promoter mutations revealed that inositol induction required a distal E-box in the CIT2 promoter. Interestingly, deleting the INO2, INO4 genes or the cognate E-box revealed phosphate induction of CIT2 expression. This layer of expression required the two R-boxes and the Pho4p bHLH protein, which is known to be required for phosphate-specific regulation. Lastly, the data show that the Hms1p and Sgc1p bHLH proteins also play important roles in repression of CIT2-lacZ expression. Collectively, these results support the model that yeast bHLH proteins coordinate different biological pathways.

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“…In yeast, myo-inositol exerts a profound effect on the regulation of gene expression. 23 Many of the genes that encode components of the PI pathway have been cloned in yeast, and regulation of inositol metabolism in yeast is understood at a molecular level. 24 The genes for inositol biosynthesis in yeast are depicted in Figure 1.…”

Section: Introductionmentioning

confidence: 99%

“…Inositol is a key metabolic sensor, and inositol levels play a major role not only in regulating inositol biosynthesis, but also in regulation of phospholipid biosynthesis and in the glucose and unfolded protein response pathways. 23 Depletion of intracellular inositol leads to the derepression of many genes that are required for inositol and phospholipid biosynthesis. 24 Conservation of function has been demonstrated from yeast to humans, and homologs of the yeast genes INO1 and INM1 are present in the human genome.…”

Section: Introductionmentioning

confidence: 99%

Epi-inositol regulates expression of the yeast INO1 gene encoding inositol-1-P synthase

Shaldubina

Vaden

et al. 2002

Mol Psychiatry

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Myo-inositol exerts behavioral effects in animal models of psychiatric disorders and is effective in clinical trials in psychiatric patients. Interestingly, epi-inositol exerts behavioral effects similar to myo-inositol, even though epi-inositol is not a substrate for synthesis of phosphatidylinositol. We postulated that the behavioral effects of epi-inositol may be due to its effects on gene expression. Yeast INO1 expression was measured in northern blots. INM1 was determined by ␤-galactosidase activity in a strain containing the fusion gene INM1-lacZ integrated into the genome. Epi-inositol affects regulation of expression of the INO1 gene (encoding inositol-1-P synthase), even though it cannot support growth of an inositol auxotroph (suggesting that, as in mammalian cells, it is not incorporated into phosphatidylinositol). Like myo-inositol, although to a lesser extent, epi-inositol causes a significant reduction in INO1 expression, and reverses the lithium-or valproate-induced increase in INO1 expression. However, it does not affect regulation of INM1 (encoding inositol monophosphatase), the expression of which is up-regulated by myo-inositol. The observed regulatory effects of epi-inositol on expression of the most highly regulated gene in the inositol biosynthetic pathway may help to explain how this inositol isomer can exert behavioral effects without being incorporated into phosphatidylinositol.

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Phospholipid biosynthesis in the yeast Saccharomyces cerevisiae and interrelationship with other metabolic processes

Cited by 306 publications

References 266 publications

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

Multiple bHLH proteins regulate CIT2 expression in Saccharomyces cerevisiae

Epi-inositol regulates expression of the yeast INO1 gene encoding inositol-1-P synthase

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