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J. Biol. Chem., Vol. 280, Issue 46, 38290-38296, November 18, 2005

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Glycerophosphocholine Catabolism as a New Route for Choline Formation for Phosphatidylcholine Synthesis by the Kennedy Pathway^*

From the Departments of Pediatrics and Biochemistry and Molecular Biology, Atlantic Research Centre, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada

In eukaryotes, neuropathy target esterase (Nte1p in yeast) deacylates phosphatidylcholine derived exclusively from the CDP-choline pathway to produce glycerophosphocholine (GroPCho) and release two fatty acids. The metabolic fate of GroPCho in eukaryotic cells is currently not known. Saccharomyces cerevisiae contains two open reading frames predicted to contain glycerophosphodiester phosphodiesterase domains, YPL110c and YPL206c. Pulse-chase experiments were conducted to monitor GroPCho metabolic fate under conditions known to alter CDP-choline pathway flux and consequently produce different rates of formation of GroPCho. From this analysis, it was revealed that GroPCho was metabolized to choline, with this choline serving as substrate for renewed synthesis of phosphatidylcholine. YPL110c played the major role in this metabolic pathway. To extend and confirm the metabolic studies, the ability of the ypl110c and ypl206c strains to utilize exogenous GroPCho or glycerophosphoinositol as the sole source of phosphate was analyzed. Consistent with our metabolic profiling, the ypl206c strain grew on both substrates with a similar rate to wild type, whereas the ypl110c strain grew very poorly on GroPCho and with moderately reduced growth on glycerophosphoinositol.

Received for publication, July 15, 2005 , and in revised form, September 16, 2005.

^* This work was supported by an operating grant from the Canadian Institutes of Health Research and a Canada Research Chair award. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Atlantic Research Centre, Dalhousie University, 5849 University Ave., Rm. C302, Halifax, Nova Scotia B3H 4H7, Canada. Tel.: 902-494-2953; Fax: 902-494-1394; E-mail: Christopher.mcmaster{at}dal.ca.

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