Comparative genomics and evolution of eukaryotic phospholipid biosynthesis

Lykidis, Athanasios

doi:10.1016/j.plipres.2007.03.003

Cited by 82 publications

(79 citation statements)

References 171 publications

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“…2) (7,10). Animals cannot de novo synthesize ethanolamine and therefore obtain it from their diet, primarily as lipids.…”

Section: Ethanolamine and Phosphatidylethanolamine Properties And Funmentioning

confidence: 99%

“…PEMTs are sporadically distributed in eukaryotes; they cannot be identified in insects, nematodes, plants, and in several unicellular protists (7). In the bacteria that do contain PC, methylation of PE by PEMTs was thought to be the only pathway for biosynthesis of PC, until the discovery of the PC synthases, which condense choline directly with CDP-DAG (12).…”

Section: Alternative Phosphatidylcholine Biosynthesismentioning

confidence: 99%

“…The Kennedy pathway enzymes are found ubiquitously in eukaryotes, with the exception of Giardia lamblia, which neither has the cytidylyltransferases nor the phosphotransferases, but does possess a C/EK, probably operating as part of a different biosynthetic pathway (7).…”

Section: Introductionmentioning

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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“…2) (7,10). Animals cannot de novo synthesize ethanolamine and therefore obtain it from their diet, primarily as lipids.…”

Section: Ethanolamine and Phosphatidylethanolamine Properties And Funmentioning

confidence: 99%

Section: Alternative Phosphatidylcholine Biosynthesismentioning

confidence: 99%

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The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

2010

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“…The pathways of de novo phospholipid biosynthesis have not been extensively studied in fish, 272 but all the necessary phospholipid biosynthetic enzymes and protein families can be found in the 273 fugu (Takifugu rubripes) and zebrafish (Danio rerio) genomes (Lykidis, 2007). The existing 274 biochemical evidence also suggests that pathways are essentially the same as in mammals 275 (Tocher, 1995).…”

Section: Phosphoinositides 179mentioning

confidence: 99%

The role of phospholipids in nutrition and metabolism of teleost fish

Tocher¹,

Bendiksen²,

Campbell³

et al. 2008

Aquaculture

481

395

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27It has been known for almost 25 years now that inclusion of intact phospholipids in the diet could 28 improve culture performance of various freshwater and marine fish species. The primary 29 beneficial effect was improved growth in both larvae and early juveniles, but also increased 30 survival rates and decreased incidence of malformation in larvae, and perhaps increased stress 31 resistance. Determination of absolute dietary requirements has been hampered by the use, in 32 different dietary trials, of a wide range of phospholipid preparations that can vary greatly both in 33 phospholipid content and class composition. Larval studies have been compromised further by the 34 need on many occasions to supply phospholipid through enrichment of live feeds with subsequent 35 re-modelling of the phospholipid and fatty acid compositions. Generally, the levels of 36 phospholipid requirement are around 2 -4% of diet for juvenile fish and probably higher in larval 37 fish. The effects were restricted to young fish, as a requirement for dietary phospholipids has not 38 been established for adult fish, although this has been virtually unstudied. As the majority of 39 studies have used crude mixed phospholipid preparations, particularly soybean lecithin, but also 40 other plant phospholipids and egg yolk lecithin, that are enriched in several phospholipids, it has 41 been difficult to elucidate which specific phospholipid classes impart beneficial effects. Based on 42 the few studies where single pure phospholipid species have been used, the rank order for efficacy 43 appears to be phosphatidylcholine > phosphatidylinositol > phosphatidylethanolamine > 44 phosphatidylserine. The efficacy of other phospholipid classes or sphingolipids is not known. The 45 mechanism underpinning the role of the phospholipids in larval and early juvenile fish must also 46 explain their lack of effect in adult fish. The role of phospholipids appears to be independent of 47 fatty acid requirements although the presence of an unsaturated fatty acid at the sn-2 position may 48 be important. Similarly, the phospholipid requirement is not related to the delivery of other 49 essential dietary components such as the bases choline and inositol. Studies also suggested that the 50 phospholipid effect was not due to generally enhanced emulsification and digestion of lipids. 51Rather the evidence led to the hypothesis that early developing stages of fish had impaired ability 52 to transport dietary lipids away from the intestine possibly through limitations in lipoprotein 53 synthesis. The current hypothesis is that the enzymic location of the limitation is actually in 54 phospholipid biosynthesis, perhaps the production of the glycerophosphobase backbone and that 55 dietary supplementation with intact phospholipids in larvae and juvenile fish compensated for this. 56

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“…In prokaryotes, PG and a phosphatidyl moiety from a second PG are condensed to CL, whereas in eukaryotes, PG and CDP-diacylglycerol are used as substrates for CL formation. The catalytic sites of almost all prokaryotic Cls contain phospholipase D (PLD)-like motifs, whereas those of eukaryotic Cls contain motifs of enzymes belonging to the CDP-alcohol phosphatidyltransferase family, such as phosphatidyland phosphotransferases (22)(23)(24).The protozoan parasite Trypanosoma brucei is the causative agent of human African sleeping sickness and nagana in domestic animals. Basic research to understand the biology of African trypanosomes to combat the deadly diseases they cause led to the discovery of several key biological processes that later were identified in other eukaryotes as well, such as antigenic variation (25), transsplicing (26), glycosylphosphatidylinositolanchoring of proteins (27), and RNA editing (28).…”

mentioning

confidence: 99%

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

Serricchio

Bütikofer

2012

Proc. Natl. Acad. Sci. U.S.A.

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Cardiolipin is important for bacterial and mitochondrial stability and function. The final step in cardiolipin biosynthesis is catalyzed by cardiolipin synthase and differs mechanistically between prokaryotes and eukaryotes. To study the importance of cardiolipin synthesis for mitochondrial integrity, membrane protein complex formation, and cell proliferation in the human and animal pathogenic protozoan parasite, Trypanosoma brucei , we generated conditional cardiolipin synthase-knockout parasites. We found that cardiolipin formation in T. brucei procyclic forms is catalyzed by a bacterial-type cardiolipin synthase, providing experimental evidence for a prokaryotic-type cardiolipin synthase in a eukaryotic organism. Ablation of enzyme expression resulted in inhibition of de novo cardiolipin synthesis, reduction in cellular cardiolipin levels, alterations in mitochondrial morphology and function, and parasite death in culture. By using immunofluorescence microscopy and blue-native gel electrophoresis, cardiolipin synthase was shown to colocalize with inner mitochondrial membrane proteins and to be part of a large protein complex. During depletion of cardiolipin synthase, the levels of cytochrome oxidase subunit IV and cytochrome c1, reflecting mitochondrial respiratory complexes IV and III, respectively, decreased progressively.

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Comparative genomics and evolution of eukaryotic phospholipid biosynthesis

Cited by 82 publications

References 171 publications

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

The role of phospholipids in nutrition and metabolism of teleost fish

An essential bacterial-type cardiolipin synthase mediates cardiolipin formation in a eukaryote

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