Phosphatidylcholine products

As already mentioned, early attempts have been focused on the enzymatic production of lecithin in lecithin liposomes (Schmidli et al, 1991). The metabolic pathway was the so-called Salvage pathway, which converts glycerol-3-phosphate to phosphatidic acid, then diacylglycerol and hnally phosphatidylcholine. Production of the cell boundary from within corresponds to autopoiesis and would close the circle between minimal cell and the autopoietic view of cellular life. 

The de novo synthesis of phosphatidylcholine requires choline. In liver, phosphatidylcholine is synthesized and enters the membranes and lipoproteins. The dc novo synthesis of phosphatidylcholine also requires 1,2-diacylglycerol. If there is insufficient choline available, phosphatidylcholine production by the de novo pathway cannot occur. The 1,2-diacylglycerol is then converted to triacylglycerol. which accumulates, as it is not secreted in lipoproteins, by the liver. Therefore, the liver cells fill with triacylglycerol. 

Fig. 5. Pathway depicting how flux through phosphatidylcholine (product of reaction 3) can promote acyl group diversity in plant triacylglycerols. Production of 18 2 (boxed) at the sn-2 position and its transfer to TG is used as a sample modification. Other fatty acid alterations may be substituted. Enzymes 1, glycerol-3-phosphate acyl-CoA acyltransferase and lysophosphatidic acid acyl-CoA acyltransferase 2, phosphatidic acid phosphatase 3, diacylglyceroliCDP-aminoalcohol aminoalcoholphosphotransferase 4, 18 l-desaturase or other fatty acid modifying enzyme 5, phosphlipid diacylglycerol acyltransferase 6, diacylglycerol acyltransferase 7, acyl-CoA phosphatidylcholine acyltransferase or phospholipase plus acyl-CoA synthetase.

Gunther, B. R. (1984) Process for the separation of oil and/or phosphatidylethanolamine from alcohol soluble phosphatidylcholine products, containing the same. United States Patent... 

Diacylglycerol is glycerol esterified to two fatty acids at the sn-1 and sn-2 positions. It is a membrane-embedded product of phospholipase C action and an activator of protein kinase C. It is also an intermediate in the biosynthesis of triacylglycerol, phosphatidyletha-nolamine and phosphatidylcholine. 

Phosphatidylcholine, commonly known as lecithin, is the most commonly occurring in natnre and consists of two fatty add moieties in each molecule. Phosphati-dylethanolamine, also known as cephahn, consists of an amine gronp that can be methylated to form other compounds. This is also one of the abundant phospholipids of animal, plant, and microbial origin. Phosphatidylserine, which has weakly acidic properties and is found in the brain tissues of mammals, is found in small amounts in microorganisms. Recent health claims indicate that phosphatidylserine can be used as a brain food for early Alzheimer s disease patients and for patients with cognitive dysfunctions. Lysophospholipids consist of only one fatty acid moiety attached either to sn-1 or sn-2 position in each molecule, and some of them are quite soluble in water. Lysophosphatidylchohne, lysophosphatidylserine, and lysophos-phatidylethanolamine are found in animal tissues in trace amounts, and they are mainly hydrolytic products of phospholipids. 

The rate of production of DAG in the cell does not occur linearly with time, but rather it is biphasic. The first peak is rapid and transient and coincides with the formation of IP3 and the release of Ca2+ this DAG is therefore derived from the PI-PLC catalyzed hydrolysis of phosphatidylinositols [1]. There is then an extended period of enhanced DAG production that is now known to be derived from the more abundant phospholipid phosphatidylcholine (PC), which has a different composition of fatty acid side chains [9]. Although DAG may be generated directly from PC through the action of PC-PLC, it can also be formed indirectly from PC. In this pathway, PC is first hydrolyzed by PLD to give choline and phosphatidic acid, which is then converted to DAG by the action of a phos-phatidic acid phosphatase [10,11 ]. 

A more successful strategy for developing sensitive and facile assays to monitor PLCBc activity involves converting the phosphorylated headgroup into a colorimetric agent via a series of enzyme coupled reactions. For example, phosphatidylcholine hydrolysis can be easily monitored in a rapid and sensitive manner by enzymatically converting the phosphorylcholine product into a red dye through the sequential action of alkaline phosphatase, choline oxidase, and peroxidase [33]. This assay, in which 10 nmol of phosphorylcholine can be readily detected, may be executed in a 96-well format and has been utilized in deuterium isotope and solvent viscosity studies [34] and to evaluate inhibitors of PLCBc [33] and site-directed mutants of PLCBc [35,36]. 

Rudolf and Cliff [3.43] described the inclusion of hemoglobin in liposomes (LEH), to produce a stable blood substitute. The liposomes were formed from a solution of soya bean - phosphatidylcholine (soy PC), cholesterol, dimyristoyl-phosphatidyl, DL-glycerol (DMPG), and alpha-tocopherol with a ratio of 10 9 0.9 0.1. The product was dried and... 

As mentioned above, PAF and PAF-like molecules are rapidly synthesized by keratinocytes following UV exposure. We suggest that two mechanisms are involved. UV-induced free radical formation leads to membrane oxidation and the formation of oxidized phosphatidylcholine. The PAF-like molecules bind to PAF receptors in either a paracrine or autocrine fashion. This induces the release of arachidonic acid from the membrane, activates PI.A2 and promotes the synthesis of bona fide PAF.55 The newly synthesized PAF then binds to PAF receptors, which upregulates the production of more PAF and downstream biological modifiers such as eicosanoids and cytokines. Ultimately this activates the cascade of events that leads to immune suppression. 

Figure 6.16. Hydrolysis of phosphatidylcholine by phospholipase A2. This reaction yields two important products arachidonic acid and lyso-PAF.

Figure 6.19. Products of phosphatidylcholine metabolism. Phosphatidylcholine is metabolised to phosphatidic acid via the activity of phospholipase D. The phosphatidic acid generated in this way may then be converted into diacylglycerol via phosphatidate phospho-hydrolase (which is inhibited by propranolol), and the enzyme diacylglycerol kinase may regenerate the phosphatidic acid. Phospholipase D may also catalyse the transphosphati-dylation of primary alcohols, such as ethanol and butanol, at the expense of the natural substrate, phosphatidylcholine. Thus, primary alcohols can prevent phosphatidic acid production via this route.

Figure 1. Control of mitochondrial biogenesis by the nuclear genome. Most mitochondrial proteins, including cytochrome c, are nuclear gene products which are subsequently imported into mitochondria. Similarly, most enzymes involved in synthesis of mitochondrial phosphoplipids are encoded in the nuclear genome. Being located in the endoplasmatic reticulum, they synthesize phosphatidylcholine (PtdCho), phosphatidylserine (PtdSer), phosphatidylglycerol (PG) and phosphatidylinositol (Ptdins). The phospholipids are transferred to the outer membrane. The imported lipids then move into the inner membrane at contact sites. Mitochondria then diversify phospholipids. They decarboxylate phosphatidylserine to phosphatidylethanolamine (PtdEtN), but the main reaction is the conversion of imported phosphatidylglycerol to cardiolipin (CL). Cardiolipins localize mainly in the outer leaflet of the inner membrane.

Teige, B., T. T. McManus, and J. B. Mudd. Reaction of ozone with phosphatidylcholine liposomes and the lytk effect of products on red blood cells. Chem. Phys. Upids 12 153-171, 1974. 

Ma LY, LaCagnin LB, Bowman L, et al. 1989. Carbon tetrachloride inhibits synthesis of pulmonary surfactant disaturated phosphatidylcholines and ATP production in alveolar type II cells. Acta Biochem Biophys 1003 136-144. 

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