Abstract
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) alpha die during embryogenesis, whereas mice that lack CKbeta unexpectedly develop muscular dystrophy. Mice that lack CTP:phosphocholine cytidylyltransferase (CT) alpha also die during early embryogenesis, whereas mice that lack CTbeta exhibit gonadal dysfunction. The cytidylyltransferase beta 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.
Highlights
Phosphatidylcholine (PC) is made in mammalian cells from choline via the CDP-choline pathway
Choline kinase Dietary choline is absorbed by the intestine in the form of lysophosphatidylcholine or choline, and uptake of the latter is mediated by choline transporters [14]
The lack of understanding of how the lack of CKb could lead to muscular dystrophy reflects the almost complete lack of knowledge about PC biosynthesis and metabolism in muscle
Summary
Choline kinase Dietary choline is absorbed by the intestine in the form of lysophosphatidylcholine or choline, and uptake of the latter is mediated by choline transporters [14]. The phosphorylation of choline is catalyzed by choline kinase (CK). CKa1 and CKa2 are encoded by Chka on mouse chromosome 19 [16]. CKb is encoded by Chkb, which is located. Copyright D 2008 by the American Society for Biochemistry and Molecular Biology, Inc. This article is available online at http://www.jlr.org. Mice that lack CKb are viable but develop rostrocaudal muscular dystrophy and neonatal bone deformity [18]. The connection between PC synthesis and muscular dystrophy in Chkb2/2 mice remains unclear. The lack of understanding of how the lack of CKb could lead to muscular dystrophy reflects the almost complete lack of knowledge about PC biosynthesis and metabolism in muscle. CKb contains 394 amino acids, and the sequence is 60% similar to that of CKa1. The CKs can exist as either homodimers or heterodimers [16]
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