Phosphoglycerides can be made using CDPbases

As can be seen in Fig. 7.1, diacylglycerol generated by phosphatidate phosphohydrolase can have several fates, one of which is to be used for generation of the zwitterionic phosphoglycerides, phosphatidylcholine and phosphatidylethanola-mine. In animals and plants the CDP-base pathway is the main pathway for production of phosphati-dylcholine, which represents 40-50% of the total lipids in most of their membranes.

Three enzymic steps are used (Fig. 7.2). First, the base (either choline or ethanolamine) is phos-phorylated by a kinase that uses ATP. In most tissues, including those from animals, plants and the yeast Saccharomyces cerevisiae, separate choline and ethanolamine kinases are found. In fact, in yeast the genes for these enzymes have been mapped to separate chromosomes. However, some choline kinases do have limited activity with the alternative ethanolamine substrate.

The second enzyme in the pathway is a cytidy-lyltransferase, which links the phosphorylated base to CMP to create CDP-choline or CDP-ethanola-mine. In those tissues where phosphatidylcholine synthesis has been studied in detail, the cytidylyl-transferase seems to be important in regulating the overall rate of phospholipid formation. This includes the initiation of lung surfactant synthesis (Section 7.7), indole 3-acetic acid-induced plant growth and the formation of Golgi-derived secretory vesicles in yeast. In animals, the cytidylyl-transferase contains lipid binding and phosphorylation domains. Near the N-terminus is a nuclear localization signal. Although the enzyme tends to be mainly soluble (cytoplasmic) it will associate with membranes, including the nuclear envelope, when it is activated. Binding of phos-pholipids and phosphorylation at a number of sites activate the cytidylyltransferase.

In plants choline phosphate cytidylyltransferase activity was increased long term by gene expression, as well as short term by activation. Of the factors identified as being important, CTP and AMP concentrations were significant. This was interesting because, in yeast, the supply of CTP (by CTP synthetase) was also found to stimulate the formation of phosphatidylcholine.

The CDP-choline or CDP-ethanolamine produced by the cytidylyltransferases are rapidly utilized by phosphotransferase enzymes, which release CMP and transfer the phosphorylated base to diacylglycerol. The phosphotransferases are integral membrane proteins and the ethanolamine-phosphotransferase has never been purified from any source. However, from selectivity experiments with different diacylglycerols or by examining the molecular species of phosphatidylethanolamine or phosphatidylcholine formed, separate phospho-transferase enzymes seem to be present in both animals and plants. In yeast, the genes for these two individual phosphotransferases have been isolated.

As well as being involved in the production of phosphatidylcholine, CDP-choline can be used for the formation of the sphingosine-containing phos-pholipid, sphingomyelin (Section 6.3). However, the major pathway for the formation of sphingo-myelin transfers phosphorylcholine from phos-phatidylcholine to a ceramide (Section 7.4.6).

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  • jussi
    How are phosphoglycerides made?
    8 years ago

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