Glycerophosphocholine catabolism as a new route for choline formation for phosphatidylcholine synthesis by the Kennedy pathway.
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 ypl110cDelta and ypl206cDelta strains to utilize exogenous GroPCho or glycerophosphoinositol as the sole source of phosphate was analyzed. Consistent with our metabolic profiling, the ypl206cDelta strain grew on both substrates with a similar rate to wild type, whereas the ypl110cDelta strain grew very poorly on GroPCho and with moderately reduced growth on glycerophosphoinositol.
Fernández-Murray
J Pedro
JP
Department of Pediatrics, Atlantic Research Centre, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada.
McMaster
Christopher R
CR
D001671:Biochemistry / Q000379:methods; D002794:Choline / Q000737:chemistry*; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D005997:Glycerylphosphorylcholine / Q000378:metabolism*; D007294:Inositol / Q000737:chemistry; D008956:Models, Chemical; D016366:Open Reading Frames; D010710:Phosphates / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry*; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000502:physiology*; D013696:Temperature; D013997:Time Factors
D005227:Fatty Acids; D010710:Phosphates; D010713:Phosphatidylcholines; D029701:Saccharomyces cerevisiae Proteins; D007294:Inositol; D003566:Cytidine Diphosphate Choline; D005997:Glycerylphosphorylcholine; D010727:Phosphoric Diester Hydrolases; C506775:Ypl110c protein, S cerevisiae; C506776:Ypl206c protein, S cerevisiae; D005947:Glucose; D002794:Choline