differential role of human choline kinase α and β enzymes in lipid metabolism implications in cancer onset and treatment微分作用人类胆碱激酶α和β的酶在癌症发病和治疗脂质代谢的影响.pdfVIP

Differential Role of Human Choline Kinase a and b Enzymes in Lipid Metabolism: Implications in Cancer Onset and Treatment 1 1,2 1,2 1 David Gallego-Ortega , Ana Ramirez de Molina , Maria Angeles Ramos , Fatima Valdes-Mora , Maria Gonzalez Barderas3, Jacinto Sarmentero-Estrada1,2, Juan Carlos Lacal1,2* ´ ´ 1Translational Oncology Unit, CSIC-UAM-La Paz, Instituto de Investigaciones Biomedicas, Madrid, Spain, 2 TCD Pharma, Centro Nacional de Biotecnologıa, Madrid, Spain, 3 Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos, SESCAM, Toledo, Spain Abstract Background: The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of the Kennedy branch of synthesis of phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKa and ChoKb isoforms, the first one with two different variants of splicing. Recently ChoKa has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKb in carcinogenesis has been reported. Methodology/Principal Findings: Here we compare the in vitro and in vivo properties of ChoKa1 and ChoKb in lipid metabolism, and their potential role in carcinogenesis. Both ChoKa1 and ChoKb showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for