Molecular cloning of mouse choline kinase and choline/ethanolamine kinase: their sequence comparison to the respective rat homologs

Aoyama, Chieko; Nakashima, Kinichi; Ishidate, Kozo

doi:10.1016/s0005-2760(98)00062-9

Cited by 28 publications

(22 citation statements)

References 16 publications

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“…Rat CKI3 has been expressed in E. coli and demonstrated to encode an enzyme that phosphorylates choline with a 6-fold higher specific activity than ethanolamine (14). Two CKI clones from mouse embryo are homologous with the two rat genes (28). Therefore, there are at least two genes encoding CKI in rat and mouse, although only one human CKI has been characterized thus far (29).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of a Mammalian Ethanolamine-specific Kinase Accelerates the CDP-ethanolamine Pathway

Lykidis¹,

Wang²,

Karim³

et al. 2001

Journal of Biological Chemistry

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Ethanolamine kinase (EKI) is the first committed step in phosphatidylethanolamine (PtdEtn) biosynthesis via the CDP-ethanolamine pathway. We identify a human cDNA encoding an ethanolamine-specific kinase EKI1 and the structure of the EKI1 gene located on chromosome 12. EKI1 overexpression in COS-7 cells results in a 170-fold increase in ethanolamine kinase-specific activity and accelerates the rate of [ 3 H]ethanolamine incorporation into PtdEtn as a function of the ethanolamine concentration in the culture medium. Acceleration of the CDP-ethanolamine pathway does not result in elevated cellular PtdEtn levels, but rather the excess PtdEtn is degraded to glycerophosphoethanolamine. EKI1 has negligible choline kinase activity in vitro and does not influence phosphatidylcholine biosynthesis. Acceleration of the CDP-ethanolamine pathway also does not change the rate of PtdEtn formation via the decarboxylation of phosphatidylserine. The data demonstrate the existence of separate ethanolamine and choline kinases in mammals and show that ethanolamine kinase can be a rate-controlling step in PtdEtn biosynthesis.Ethanolamine kinase or EKI 1 (ATP:ethanolamine O-phosphotransferase, EC 2.7.1.82) catalyzes the first step of PtdEtn biosynthesis via the CDP-Etn pathway. ECT, a cytidylyltransferase, and EPT, an amino alcohol phosphotransferase, catalyze the subsequent two steps, and together these three enzymes constitute the de novo pathway for PtdEtn formation. The decarboxylation of PtdSer is an alternate route for PtdEtn production and is functionally important in cultured cell lines (1, 2), although the CDP-Etn pathway is considered a major route for PtdEtn synthesis in most mammalian tissues (3-6). PtdEtn is an abundant phospholipid in eucaryotic cell membranes, and the ECT reaction is thought to be a major regulator of its synthesis (7). EKI has been proposed as a regulatory step based on theoretical considerations (8). However, experimental investigations result in conflicting conclusions. Experiments performed with rat hepatocytes (4, 9) demonstrate that the supply of ethanolamine limits the rate of PtdEtn production at concentrations below 30 M. Only at higher concentrations of ethanolamine does accumulation of phosphoethanolamine occur, indicating ECT as the rate-limiting enzyme of the pathway. On the contrary, McMaster and Choy (10) report that the EKI step is rate-limiting with increased ethanolamine concentrations using a hamster heart perfusion model. Both studies agree that the rate of PtdEtn synthesis is dependent on the extracellular ethanolamine concentration (9, 10) and that the stimulation of PtdEtn biosynthesis occurs at physiological levels of 20 -50 M (9).There is a long standing discussion as to the number and specificity of the enzymes that catalyze the phosphorylation of ethanolamine and choline. In yeast, there are two enzymes that are able to phosphorylate choline and ethanolamine, and these enzymes are annotated based on their preferred substrate specificities. The CKI enzyme has a specific activit...

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Section: Discussionmentioning

confidence: 99%

Overexpression of a Mammalian Ethanolamine-specific Kinase Accelerates the CDP-ethanolamine Pathway

Lykidis¹,

Wang²,

Karim³

et al. 2001

Journal of Biological Chemistry

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“…The first CK gene was characterized by Uchida et al [64]. Subsequently, a second gene encoding CK was identified [65,66]. Based on the dual specificity of these enzymes towards choline and ethanolamine it was considered that ethanolamine specific kinases may not exist.…”

Section: Choline and Ethanolamine Kinases (Cks And Eks)mentioning

confidence: 99%

Comparative genomics and evolution of eukaryotic phospholipid biosynthesis

Lykidis

2007

Progress in Lipid Research

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Phospholipid biosynthetic enzymes produce diverse molecular structures and are often present in multiple forms encoded by different genes. This work utilizes comparative genomics and phylogenetics for exploring the distribution, structure and evolution of phospholipid biosynthetic genes and pathways in 26 eukaryotic genomes. Although the basic structure of the pathways was formed early in eukaryotic evolution, the emerging picture indicates that individual enzyme families followed unique evolutionary courses. For example, choline and ethanolamine kinases and cytidylyltransferases emerged in ancestral eukaryotes, whereas, multiple forms of the corresponding phosphatidyltransferases evolved mainly in a lineage specific manner.Furthermore, several unicellular eukaryotes maintain bacterial-type enzymes and reactions for the synthesis of phosphatidylglycerol and cardiolipin. Also, base-exchange phosphatidylserine synthases are widespread and ancestral enzymes. The multiplicity of phospholipid biosynthetic enzymes has been largely generated by gene expansion in a lineage specific manner. Thus, these observations suggest that phospholipid biosynthesis has been an actively evolving system. 2Finally, comparative genomic analysis indicates the existence of novel phosphatidyltransferases and provides a candidate for the uncharacterized eukaryotic phosphatidylglycerol phosphate phosphatase.

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“…PCho and phosphoethanolamine are the two most abundant phospho-monoesters in cartilage [73]. CK also phosphorylates ethanolamine to phosphoethanolamine [74,75]. Possibly Chkb deficiency reduces the availability of substrates (PCho and phosphoethanolamine) for Phospho1 and thereby limits the ability of Phospho1 to produce sufficient inorganic phosphate (Pi) for cartilage mineralization.…”

Section: Discussionmentioning

confidence: 99%

Choline kinase beta is required for normal endochondral bone formation

Sher

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background Choline kinase has three isoforms encoded by the genes Chka and Chkb. Inactivation of Chka in mice results in embryonic lethality, whereas Chkb−/− mice display neonatal forelimb bone deformations. Methods To understand the mechanisms underlying the bone deformations, we compared the biology and biochemistry of bone formation from embryonic to young adult wild-type (WT) and Chkb−/− mice. Results The deformations are specific to the radius and ulna during the late embryonic stage. The radius and ulna of Chkb−/− mice display expanded hypertrophic zones, unorganized proliferative columns in their growth plates, and delayed formation of primary ossification centers. The differentiation of chondrocytes of Chkb−/− mice was impaired, as was chondrocyte proliferation and expression of matrix metalloproteinases 9 and 13. In chondrocytes from Chkb−/− mice, phosphatidylcholine was slightly lower than in WT mice whereas the amount of phosphocholine was decreased by approximately 75%. In addition, the radius and ulna from Chkb−/− mice contained fewer osteoclasts along the cartilage/bone interface. Conclusions Chkb has a critical role in the normal embryogenic formation of the radius and ulna in mice.

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Molecular cloning of mouse choline kinase and choline/ethanolamine kinase: their sequence comparison to the respective rat homologs

Cited by 28 publications

References 16 publications

Overexpression of a Mammalian Ethanolamine-specific Kinase Accelerates the CDP-ethanolamine Pathway

Overexpression of a Mammalian Ethanolamine-specific Kinase Accelerates the CDP-ethanolamine Pathway

Comparative genomics and evolution of eukaryotic phospholipid biosynthesis

Choline kinase beta is required for normal endochondral bone formation

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