Choline kinase, reaction catalyzed

The CT reaction usually limits the rate of PC biosynthesis. The first evidence in support of this conclusion was drawn from the relative pool sizes of the aqueous precursors (in rat liver, choline = 0.23 mM, phosphocholine =1.3 mM, CDP-choline = 0.03 mM). Calculation of these values assumes that 1 g wet tissue is equivalent to 1 ml and that there is no compartmentation of the pools. The second assumption may not be valid as there is evidence for compartmentation of PC precursors (M.W. Spence, 1989). The concentration of phosphocholine is 40-fold higher than that of CDP-choline, consistent with a bottleneck in the pathway at the reaction catalyzed by CT. Pulse-chase experiments illustrate this bottleneck more vividly. After a 0.5 h pulse of hepatocytes with [methyl- H]choline, more than 95% of radioactivity in the precursors of PC was in phosphocholine, with the remainder in choline and CDP-choline. When the radioactivity was chased with unlabeled choline, labeled phosphocholine was quantitatively converted to PC (Fig. 5). The radioactivity in CDP-choline remained low during the chase and CDP-choline was rapidly converted to PC. There was minimal radioactivity in choline which suggests that choline is immediately phosphorylated after it enters the cell. It is important to note that if a cell or tissue is in a steady state, pool sizes and reaction rates do not change. Thus, although the rate of PC synthesis is determined by the CT reaction, the rates of the reactions catalyzed by choline kinase and cholinephosphotransferase are the same as that of the reaction catalyzed by CT, otherwise, the pool sizes of precursors would change. For example, if the choline kinase reaction were faster than the CT reaction, the amount of phosphocholine would increase. Thus, CT sets the pace of the pathway. 

Synthesis of phosphatidylcholine. The rate-limiting reaction is that catalyzed by cytidylyltransferase (reaction 2) which appears to be active only when attached to the endoplasmic reticulum, although it is also found free in the cytosol. Cytidylyltransferase is inactivated by a cAMP-dependent protein kinase and activated by a phosphatase. Translocation to the endoplasmic reticulum can be stimulated by substrates such as fatty acyl Coenzyme A (CoA). Choline deficiency can result in deposition of triacylglycerol in liver and reduced phospholipid synthesis. Enzymes (1) choline kinase ... 

Choline kinase catalyzes the reaction that follows ... 

The reaction catalyzed by choline kinase (E.C. 2.7.1.32 ATPtchollnephosphotransferase) is the first committed reaction of the nucleotide pathway for phosphatidylcholine (PtdCho) biosynthesis. Various theoretical considerations have led to the suggestion that this reaction is far from equilibrium and, along with the cytldylyltransferase reaction, may be rate-limiting for PtdCho biosynthesis in some animal tissues (1). As part of our studies on the regulation of PtdCho biosynthesis in plants we have investigated the properties of this enzyme and the in vivo concentrations of metabolites Involved in the reaction in postgermlnatlon castor bean endosperm. 

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