Glycerophosphocholine catabolism as a new route for choline formation for phosphatidylcholine synthesis by the Kennedy pathway
Glycerophosphocholine catabolism as a new route for choline formation for phosphatidylcholine synthesis by the Kennedy pathway
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DOI：
10.1074/jbc.m507700200
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发表时间：
2005-11-18
影响因子：
4.8
通讯作者：
McMaster, CR
中科院分区：
文献类型：
--
作者：
Fernández-Murray, JP;McMaster, CR
在真核生物中，神经病靶向酯酶（酵母中的Nte 1 p）使仅来自CDP-胆碱途径的磷脂酰胆碱脱酰，产生甘油磷酸胆碱（GroPCho）并释放两种脂肪酸。GroPCho在真核细胞中的代谢命运目前尚不清楚。酿酒酵母含有两个开放阅读框，预测其含有甘油磷酸二酯磷酸二酯酶结构域YPL 110 c和YPL 206 c。进行脉冲追踪实验以在已知改变CDP-胆碱途径通量并因此产生不同的GroPCho形成速率的条件下监测GroPCho代谢命运。从该分析中，揭示了GroPCho被代谢为胆碱，该胆碱用作磷脂酰胆碱的重新合成的底物。YPL 110 c在该代谢途径中起主要作用。为了扩展和确认代谢研究，分析了ypl 110 c Delta和ypl 206 c Delta菌株利用外源GroPCho或甘油磷酸肌醇作为磷酸盐唯一来源的能力。与我们的代谢谱一致，ypl 206 c Delta菌株在两种底物上以与野生型相似的速率生长，而yplllOc Delta菌株在GroPCho上生长非常差，并且在甘油磷酸肌醇上生长适度降低。
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 Delta and ypl206c Delta strains to utilize exogenous GroPCho or glycerophosphoinositol as the sole source of phosphate was analyzed. Consistent with our metabolic profiling, the ypl206c Delta strain grew on both substrates with a similar rate to wild type, whereas the ypl110c Delta strain grew very poorly on GroPCho and with moderately reduced growth on glycerophosphoinositol.