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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.R800048-JLR200 on October 27, 2008

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Journal of Lipid Research, Vol. 50, S132-S137, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology


Metabolism

Physiological consequences of disruption of mammalian phospholipid biosynthetic genes

Dennis E. Vance1,* and Jean E. Vance1,{dagger}

* Group on Molecular and Cell Biology of Lipids and Department of Biochemistry, University of Alberta, Edmonton, Alberta T6G 2S2 Canada
{dagger} Group on Molecular and Cell Biology of Lipids and Department of Medicine, University of Alberta, Edmonton, Alberta T6G 2S2 Canada

Research in the authors' labs was supported by grants from Canadian Institutes of Health Research and Heart and Stroke Foundation. D.E.V. holds the Canada Research Chair in Molecular and Cell Biology of Lipids and is a Scientist of the Alberta Heritage Foundation for Medical Research.

Published, JLR Papers in Press, October 27, 2008.

1 To whom correspondence should be addressed. e-mail: dennis.vance{at}ualberta.ca (D.E.V.); jean.vance{at}ualberta.ca (J.V.)


ABSTRACT

By 1959, Eugene Kennedy and coworkers had outlined most pathways of phospholipid biosynthesis. In the next four decades, the emphasis was on enzymology and regulation of these pathways. In the last 12 years, several lines of mice with disrupted genes of phospholipid biosynthesis were generated. From this research, we have learned that embryonic lethality occurs in mice that lack choline kinase (CK) {alpha}, CTP:phosphocholine cytidylyltransferase {alpha}, CTP:phosphoethanolamine cytidylyltransferase, or phosphatidylserine decarboxylase. Whereas mice that lack CK β are viable but develop hindlimb muscular dystrophy and neonatal bone deformity. Mice that lack CTP:phosphocholine cytidylytransferase β have gonadal dysfunction and defective axon branching. Mice that lack phosphatidylethanolamine N-methyltransferase exhibit no phenotype until fed a choline-deficient diet, which leads to rapid liver failure. Future research should extend our knowledge about the function of these and other enzymes of phospholipid biosynthesis.

Supplementary key words phosphatidylcholine • phosphatidylethanolamine • phosphatidylserine • choline kinase • CTP:phosphocholine cytidylyltransferase • phosphatidylethanolamine N-methyltransferase • phosphatidylserine synthase • phosphatidylserine decarboxylase

Abbreviations: apo, apolipoprotein; CD, choline-deficient; CK, choline kinase; CT, CTP:phosphocholine cytidylyltransferase; ER, endoplasmic reticulum; ET, CTP:phosphoethanolamine cytidylyltransferase; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PEMT, phosphatidylethanolamine N-methyltransferase: PS, phosphatidylserine; PSD, PS decarboxylase; PSS, PS synthase; TG, triacylglycerol


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JLR 50th Anniversary Collections
Anniversary Collection:: Metabolism




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