Ethanolamine kinase

The majority of PC is synthesized in mammalian cells by the CDP-choline or Kennedy pathway in the endoplasmic reticulum (Eigiue 1). In this pathway, choline taken up from the external medium or released in the cytosol by breakdown of choline containing compoimds, is first converted to phosphocholine by the enzyme choline kinase (CK) (Ishidate, 1997). There are two isoforms of CK cloned which both can convert also ethanolamine to phosphoethanolamine, albeit with a lesser affinity (Aoyama et al 2000). Alternatively phosphocholine can be generated by enzymes that preferentially phosphorylate ethanolamine and are therefore designated ethanolamine kinases (EK). As yet also two different EKs are known (EKI 1 and 2 Lykidis etal., 2001). 

PE can be generated by several mechanisms. The CDP-ethanolamine route may be important under physiological conditions in vivo when an abundant supply of ethanolamine is present. The CDP-ethanolamine pathway is very similar to the CDP-choline pathway described above (Tijburg et al. 1989 Bladergroen and Van Golde, 1997). The pathway comprises (i) an ethanolamine kinase (EK) which converts ethanolamine to phosphoethanolamine, (ii) an CTP phosphoethanolamine cytidyltransferase... 

Aoyama, C., Yamazaki, N., Terada, H., and Ishidate, K.., 2000, Structure and characterization of the genes for murine choline/ethanolamine kinase isozymes alpha and beta. J. Lipid. Res 41 452-464... 

Houweling, M., Cui, Z., and Vance, D.E., 1995, Expression of phosphatidylethanolamine N-methyltransferase-2 cannot compensate for an impaired CDP-choUne pathway in mutant Chinese hamster ovary cells. J. Biol. Chem. 270 16277-16282 Ishidate, K.. 1997, Chohne/ethanolamine kinase from mammalian tissues. Biochim. Biophys. Acta 1348 70-78... 

CARNOSINE SYNTHETASE CHAPERONES CHOLINE KINASE CHOLOYL-CoA SYNTHETASE COBALAMIN ADENOSYLTRANSFERASE 4-COUMAROYL-CoA SYNTHETASE CREATINE KINASE CTP SYNTHETASE CYTIDYLATE KINASE 2-DEHYDRO-3-DEOXYGLUCONOKINASE DEHYDROGLUCONOKINASE DEOXYADENOSINE KINASE DEOXYADENYLATE KINASE DEOXYCYTIDINE KINASE (DEOXYjNUCLEOSIDE MONOPHOSPHATE KINASE DEOXYTHYMIDINE KINASE DEPHOSPHO-CoA KINASE DETHIOBIOTIN SYNTHASE DIACYLGLYCEROL KINASE DIHYDROFOLATE SYNTHETASE DNA GYRASES DNA REVERSE GYRASE ETHANOLAMINE KINASE EXONUCLEASE V... 

ETHANOLAMINE AMMONIA-LYASE ETHANOLAMINE KINASE CHOLINE KINASE... 

Although the role of lipid composition in membrane function is not entirely understood, changes in composition can produce dramatic effects. Researchers have isolated fruit flies with mutations in the gene that encodes ethanolamine kinase (analogous to choline kinase Fig. 21-28). Lack of this enzyme eliminates one pathway for phosphatidylethanolamine synthesis, thereby reducing the amount of this lipid in cellular membranes. Flies with this mutation—those with the genotype easily shocked—exhibit transient paralysis following electrical stimulation or mechanical shock that would not affect wild-type flies. 

The second phase of phospholipid synthesis in eukaryotes. Choline or ethanolamine enters the cell via active transport mechanisms and is immediately phosphorylated by the enzyme, choline (ethanolamine) kinase. The phosphorylated derivatives of choline and ethanolamine... 

Phosphatidylcholine is preferentially synthesized in lactating mammary tissue (Kinsella, 1973), possibly regulated by the differential activities of choline kinase and ethanolamine kinase. Choline kinase has a lower Km and a higher Vmax with its substrate than does ethanolamine kinase. Also, choline kinase is inhibited slightly by ethanolamine, whereas choline is a potent competitive inhibitor of ethanolamine kinase. Thus, the intracellular concentration of choline probably regulates the synthesis of these two phos-phoglycerides (Infante and Kinsella, 1976). 

Infante, J.P., Kinsella, J.E. 1976. Phospholipid synthesis in mammary tissue. Choline and ethanolamine kinases Kinetic evidence for two discrete active sites. Lipids 11, 727-735. 

Phosphatidylethanolamines, or cephalins (so-called because they were first obtained from brain tissue), can be synthesized by reactions analogous to those of de novo synthesis of phosphatidylcholine. Ethanolamine is first phosphorylated by ATP and ethanolamine kinase to phosphoethanolamine, which then reacts with CTP to form CDP-ethanolamine. CTPrphosphoethanolamine cytidylyltransferase is not located on the endoplasmic reticulum, nor do fatty acids activate it as they do the analogous enzyme of phosphatidylcholine synthesis. Finally, 1,2-diacylglycerol phosphoethanolamine transferase catalyses the reaction of diacylglycerol with CDP-ethanolamine to form phosphatidylethanolamine. 

Fig. 1. Phospholipid biosynthetic pathways in animal cells. The abbreviations are DHAP, dihydroxyacetone phosphate G-3-P, glycerol-3-phosphate PA, phosphatidic acid DG, diacylglycerol CDP-DG, cytidine diphosphodiacylglycerol PI, phosphatidylinositol PG, phosphatidylglycerol PG-P, phosphatidylglycerol phosphate DPG, diphosphatidylglycerol PP, phosphatidic acid phosphatase PE, phosphatidylethanolamine PC phosphatidylcholine PEMT, phosphatidylethanolamine A-methyltransferase CT, CTP phosphocholine cytidylyltransferase PS, phosphatidylserine CK/EK, choline/ethanolamine kinase CPT, CDP-choline 1,...

Mouse Etnk2 Ethanolamine kinase Placental thrombosis, neonatal lethality... 

Fig. 7. Pathways for the biosynthesis of phosphatidylethanolamine (PE) and phosphatidylseiine (PS) in animals. The numbers indicate the enzymes. 1, ethanolamine kinase 2, CTP phosphoethanolamine cytidylyltransferase 3, CDP-ethanolamine l,2-diacylglycerol ethanolaminephosphotransferase 4, PS synthase-2 5, PS synthase-1 6, PS decarboxylase 7, acyl-CoA lyso-PE acyltransferase. PC, phosphatidylcholine.

Ishidate, K. 1997. Choline/ethanolamine kinase from mammalian tissues. Biochim. Biophys. Acta 1348 70-78. 

Additional information <1-8, 10, 11, 14, 17> (<14> choline kinase and ethanolamine kinase activities are mediated by 2 distinct active sites, possibly on a single protein [7] <17> choline kinase and ethanolamine kinase may not have a common active site in a single enzyme protein [8] <1-8, 10, 11, 17> choline kinase and ethanolamine kinase are 2 distinct enzymes [9, 10, 12, 14] <17> ethanolamine kinase II and choline kinase do not use a common active site [11] cf. EC 2.7.1.32) [7-12, 14[... 

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