The CDP-ethanolamine Pathway and Phosphatidylserine Decarboxylation Generate Different Phosphatidylethanolamine Molecular Species

Bleijerveld, Onno B.; Brouwers, Jos F.; Vaandrager, Arie B.; Helms, J. Bernd; Houweling, Martin

doi:10.1074/jbc.m703786200

Cited by 85 publications

(82 citation statements)

References 53 publications

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“…This interpretation is in line with a previous report showing that two different enzyme activities are responsible for the synthesis of alk-1-enyl-acyl-PE and diacyl-PE in rabbit heart membranes (41). Separate pools of PE consisting of different molecular species have also been reported in other mammalian cells (42) and yeast (43).…”

Section: Discussionsupporting

confidence: 81%

Phosphatidylethanolamine in Trypanosoma brucei Is Organized in Two Separate Pools and Is Synthesized Exclusively by the Kennedy Pathway

Signorell

Rauch

Jelk

et al. 2008

Journal of Biological Chemistry

104

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Phosphatidylethanolamine is a major phospholipid class of all eukaryotic cells. It can be synthesized via the CDP-ethanolamine branch of the Kennedy pathway, by decarboxylation of phosphatidylserine, or by base exchange with phosphatidylserine. The contributions of these pathways to total phosphatidylethanolamine synthesis have remained unclear. Although Trypanosoma brucei, the causative agent of human and animal trypanosomiasis, has served as a model organism to elucidate the entire reaction sequence for glycosylphosphatidylinositol biosynthesis, the pathways for the synthesis of the major phospholipid classes have received little attention. We now show that disruption of the CDP-ethanolamine branch of the Kennedy pathway using RNA interference results in dramatic changes in phosphatidylethanolamine, phosphatidylserine, and phosphatidylcholine. By targeting individual enzymes of the pathway, we demonstrate that de novo phosphatidylethanolamine synthesis in T. brucei procyclic forms is strictly dependent on the CDPethanolamine route. Interestingly, the last step in the Kennedy pathway can be mediated by two separate activities leading to two distinct pools of phosphatidylethanolamine, consisting of predominantly alk-1-enyl-acyl-or diacyl-type molecular species. In addition, we show that phosphatidylserine in T. brucei procyclic forms is synthesized exclusively by base exchange with phosphatidylethanolamine.

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Section: Discussionsupporting

confidence: 81%

Phosphatidylethanolamine in Trypanosoma brucei Is Organized in Two Separate Pools and Is Synthesized Exclusively by the Kennedy Pathway

Signorell

Rauch

Jelk

et al. 2008

Journal of Biological Chemistry

104

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“…The relative contribution of the PE biosynthetic pathways to cellular PE content has not been firmly established, but it appears to depend on the cell type. In rat liver/hepatocytes and hamster heart, the CDP-ethanolamine pathway has been reported to produce the majority of PE (109)(110)(111)(112). In contrast, in many types of cultured cells, .80% of PE is apparently made from the decarboxylation of PS via PSD, even when ethanolamine is provided in the culture medium as a substrate for the CDP-ethanolamine pathway (74,113,114).…”

Section: Pe Synthesismentioning

confidence: 99%

Thematic Review Series: Glycerolipids. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids

Vance

2008

Journal of Lipid Research

427

355

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Phosphatidylserine(PS)andphosphatidylethanolamine (PE) are two aminophospholipids whose metabolism is interrelated. Both phospholipids are components of mammalian cell membranes and play important roles in biological processes such as apoptosis and cell signaling. PS is synthesized in mammalian cells by base-exchange reactions in which polar head groups of preexisting phospholipids are replaced by serine. PS synthase activity resides primarily on mitochondria-associated membranes and is encoded by two distinct genes. Studies in mice in which each gene has been individually disrupted are beginning to elucidate the importance of these two synthases for biological functions in intact animals. PE is made in mammalian cells by two completely independent major pathways. In one pathway, PS is converted into PE by the mitochondrial enzyme PS decarboxylase. In addition, PE is made via the CDP-ethanolamine pathway, in which the final reaction occurs on the endoplasmic reticulum and nuclear envelope. The relative importance of these two pathways of PE synthesis has been investigated in knockout mice. Elimination of either pathway is embryonically lethal, despite the normal activity of the other pathway. PE can also be generated from a base-exchange reaction and by the acylation of lyso-PE. Cellular levels of PS and PE are tightly regulated by the implementation of multiple compensatory mechanisms.-Vance, J. E. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids.

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“…Rat hepatocytes and Chinese hamster ovary cells show a preferential synthesis of PE with mono-or diunsaturated fatty acids on the sn-2 position (84, 85 and references therein). Not only can EPTs and CEPTs use a variety of DAG and AAG species, they can also accept modified CDP-aminoalcohols as substrates, that is, yeast EPT1 can use CDP-N-methylethanolamine, and CPT1 can convert CDP-N,N-dimethylethanolamine and CDP-propanolamine into the corresponding phospholipids (84).…”

Section: The Ctp:phosphocholine Cytidylyltransferasementioning

confidence: 99%

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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The CDP-ethanolamine Pathway and Phosphatidylserine Decarboxylation Generate Different Phosphatidylethanolamine Molecular Species

Cited by 85 publications

References 53 publications

Phosphatidylethanolamine in Trypanosoma brucei Is Organized in Two Separate Pools and Is Synthesized Exclusively by the Kennedy Pathway

Phosphatidylethanolamine in Trypanosoma brucei Is Organized in Two Separate Pools and Is Synthesized Exclusively by the Kennedy Pathway

Thematic Review Series: Glycerolipids. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

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