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Journal of Lipid Research, Vol. 49, 1187-1194, June 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Thematic Review

Thematic Review Series: Glycerolipids. Phosphatidylcholine and choline homeostasis

Zhaoyu Li¹ and Dennis E. Vance²

Department of Biochemistry and the Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada

Published, JLR Papers in Press, January 19, 2008.

¹ Present address of Z. Li: Department of Genetics, School of Medicine, University of Pennsylvania, 415 Curie Boulevard, CRB 570, Philadelphia, PA 19104.

² To whom correspondence should be addressed. e-mail: dennis.vance{at}ualberta.ca

Phosphatidylcholine (PC) is made in mammalian cells from choline via the CDP-choline pathway. Animals obtain choline primarily from the diet or from the conversion of phosphatidylethanolamine (PE) to PC followed by catabolism to choline. The main fate of choline is the synthesis of PC. In addition, choline is oxidized to betaine in kidney and liver and converted to acetylcholine in the nervous system. Mice that lack choline kinase (CK) die during embryogenesis, whereas mice that lack CKβ unexpectedly develop muscular dystrophy. Mice that lack CTP:phosphocholine cytidylyltransferase (CT) also die during early embryogenesis, whereas mice that lack CTβ exhibit gonadal dysfunction. The cytidylyltransferase β isoform also plays a role in the branching of axons of neurons. An alternative PC biosynthetic pathway in the liver uses phosphatidylethanolamine N-methyltransferase to catalyze the formation of PC from PE. Mice that lack the methyltransferase survive but die from steatohepatitis and liver failure when placed on a choline-deficient diet. Hence, choline is an essential nutrient. PC biosynthesis is required for normal very low density lipoprotein secretion from hepatocytes. Recent studies indicate that choline is recycled in the liver and redistributed from kidney, lung, and intestine to liver and brain when choline supply is attenuated.

Supplementary key words phosphatidylethanolamine N-methyltransferase • choline recycling • choline redistribution • phosphatidylethanolamine • lipoproteins

Abbreviations: AdoHcy, S-adenosylhomocysteine; AdoMet, S-adenosylmethionine; CD, choline-deficient; CK, choline kinase; CPT, CDP-choline:1,2-diacylglycerol cholinephosphotransferase; CT, CTP:phosphocholine cytidylyltransferase; ER, endoplasmic reticulum; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PEMT, phosphatidylethanolamine N-methyltransferase

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