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Arch Toxicol (2012) 86:13351336 DOI 10.1007/s00204-012-0898-z
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C. van Thriel
Published online: 10 July 2012 Springer-Verlag 2012
EDI3: key enzyme of choline metabolism and a possible link to chronic neurological disorders
The current issue of PNAS reports the discovery and functional characterization of EDI3, a key enzyme of choline metabolism (Stewart et al. 2012). EDI3 cleaves glycerophosphocholine to release choline and glycerol-3-phosphate. This represents a critical step, which provides membrane phospholipids essential for the activation of several signalling pathways. The reaction as such was already known as the Kennedy pathway. However, a key enzymatic protein positioned at the start of this pathway remained unidentiedand was now discovered to be EDI3 (Stewart et al. 2012).
The current study of Stewart and colleagues was part of a larger programme aimed at identifying prognostic markers and biomarkers of metastasis in cancer (Schmidt et al. 2008, 2009, 2011, 2012; Kammers et al. 2011; Cadenas et al. 2010, 2011; Petry et al. 2010; Tanner et al. 2006; Brase et al. 2010; Hellwig et al. 2010). EDI3 was shown to be associated with increased metastatic capacity of endometrial carcinomas (Stewart et al. 2012). This effect is mediated by the activation of PKCa which leads to enhanced tumour cell migration. This is certainly of high interest in the eld of cancer research and identies EDI3 as a promising therapeutic target.
However, the focus of Stewart et al. (2012) on tumour biology should not detract from EDI3s possible role in toxicity pathways. Recently, choline metabolism was
reported to be inuential in chronic neurological disorders induced by neurotoxic organophosphates (Hou et al. 2009), which are components of pesticides and industrial additives. Exposure to neurotoxic organophosphates leads to acute toxicity, because of the inhibition of acetylcholinesterase (Hou et al. 2009; Solberg and Belkin 1997). However, some...