Phospholipids phosphatidylserine

The negatively charged phospholipid phosphatidylserine is asymmetrically distributed in mammalian cell membranes, primarily on the inner leaflet. Upon exposure to collagen or thrombin, the distribution of phospholipids changes with increasing phosphatidylserine in the external membrane leaf (I). The increased expression of phosphatidylserine on the outer leaflet of the membrane creates a procoagulant surface on which several steps of the coagulation cascade take place. 

Phospholipid (Phosphatidylserine) FIGURE 2.32 Stmctures of triglycerides and phospholipids. 

PKC is one member of a femily of serine and threonine kinases - so-called because they catalyse the phosphorylation fix)m ATP of serine and threonine amino acid bases found in many different proteins. PKC is distinguished from other protein kinases because it is dependent on Ca and also the phospholipid phosphatidylserine (PS) for activity. When DAG appears free in the plasma membrane, quiescent PKC translocates from the cytosol to the plasma membrane, binding at sites rich in PS. It is this binding of PKC to membrane PS, in the presence of DAG, which confers increased Ca sensitivity to the enzyme and allows release of the catalytic subunit of PKC into the cytosol where target protein phosphorylation... 

In Table 3 the fatty acid composition of mitochondrial phospholipids is presented. Slight changes were detected in the fatty acid moiety of the phospholipids. Phosphatidylserine contains larger proportions of 18 0 at gastrula stage, A decrease in the relative... 

Among individual phospholipids, phosphatidylserine was the most active component (Table 1). 

Figure 4. Analysis of the different polyphosphoinositides extracted from P-labelled cells. (A) Schematic representation of the expected separation of a mixture of P-labelled phospholipids by thin layer chromatography (TLC). Plates are silica gel 60 and the solvent for phosphoinositide separation is a mixture of CHCI3, CH3COCH3, CH3OH, CH3COOH and H O (80 30 26 24 14, v/v). MP, major phospholipids (phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine). (B) Typical high-performance liquid chromatography profile showing the separation of the various phosphoinositides from a mixture of P-labelled phosphoinositides. A specific gradient must be used to separate PtdIns(4)P and PtdIns(5)P (Rameh et ai, 1997 Niebhur et al., 2002).

Mammals synthesize phosphatidylserine (PS) in a calcium ion-dependent reaction involving aminoalcohol exchange (Figure 25.21). The enzyme catalyzing this reaction is associated with the endoplasmic reticulum and will accept phosphatidylethanolamine (PE) and other phospholipid substrates. A mitochondrial PS decarboxylase can subsequently convert PS to PE. No other pathway converting serine to ethanolamine has been found. 

There is also inside-outside (transverse) asymmetry of the phospholipids. The choline-containing phospholipids (phosphatidylcholine and sphingomyelin) are located mainly in the outer molecular layer the aminophospholipids (phosphatidylserine and phos-phatidylethanolamine) are preferentially located in the inner leaflet. Obviously, if this asymmetry is to exist at all, there must be limited transverse mobility (flip-flop) of the membrane phospholipids. In fact, phospholipids in synthetic bilayers exhibit an extraordinarily slow rate of flip-flop the half-life of the asymmetry can be measured in several weeks. However, when certain membrane proteins such as the erythrocyte protein gly-cophorin are inserted artificially into synthetic bilayers, the frequency of phospholipid flip-flop may increase as much as 100-fold. 

The major lipid classes are phospholipids and cholesterol the major phospholipids are phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) along with sphingomyelin (Sph). 

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. 

FIGURE 12.4 (A) Diagrammatic representation of the separation of major simple lipid classes on silica gel TLC — solvent system hexane diethylether formic acid (80 20 2) (CE = cholesteryl esters, WE = wax esters, HC = hydrocarbon, EEA = free fatty acids, TG = triacylglycerol, CHO = cholesterol, DG = diacylglycerol, PL = phospholipids and other complex lipids). (B) Diagrammatic representation of the separation of major phospholipids on silica gel TLC — solvent sytem chloroform methanol water (70 30 3) (PA = phosphatidic acid, PE = phosphatidylethanolamine, PS = phosphatidylserine, PC = phosphatidylcholine, SPM = sphingomyelin, LPC = Lysophosphatidylcholine). 

Two routes to phospholipid biosynthesis are known in either, the participation of CTP is necessary. The first route involves phosphatidic acid in phosphoglyceride biosynthesis. Phosphatidic acid reacts with CTP to yield CDP-diglyceride which, as a coenzyme, can participate in the transfer of diglyceride onto serine (or inositol) to produce phosphatidylserine (or phosphatidylinositol). Serine phosphatides are liable to decarboxylation (pyridoxal phosphate acting... 

Today s mitochondria lack most of the genes involved in phosphohpid metabolism. Therefore, mitochondria have to import most of their hpids. Phospholipids such as phosphatidylcholine, phosphatidylserine, phosphatidylglycerol, and phosphatidylinositol must be synthesized in the endoplasmatic reticulum under the control of nuclear genes and then transferred to mitochondria (Voelker, 2000) (Figure 1). Mitochondria use both nuclear and mitochondrial encoded proteins to further diversify phospholipids (Dowhan, 1997 Kent, 1995 Daum, 1985). Thus, a nuclear phosphatidylserine decarboxylase converts phosphatidylserine into phosphatidylethanolamine, or mitochondrial encoded cardiolipin synthase converts phosphatidylglycerol into cardiolipin which is incorporated exclusively into the inner mitochondrial membrane. 

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