Cell phospholipid biosynthesis

Lecithins and related phospholipids usually contain a saturated fatty acid in the C-l position but an unsaturated acid, which may contain from one to four double bonds, at C-2. Arachidonic acid is often present here. Hydrolysis of the ester linkage at C-2 yields a l-acyl-3-phosphoglycerol, better known as a Iysophosphatidylcholine. The name comes from the powerful detergent action of these substances which leads to lysis of cells. Some snake venoms contain phospholipases that form Iysophosphatidylcholine. Lysophosphatidic acid (l-acyl-glycerol-3-phosphate) is both an intermediate in phospholipid biosynthesis (Chapter 21) and also a signaling molecule released into the bloodstream by activated platelets.15... 

Aitken, J.F., vanHeusden, G.P., Temkin, M., and Dowhan, W., 1990, The gene encoding the phosphatidylinositol transfer protein is essential for cell growth. J. Biol. Chem. 265 4711 —4717. Ambroziak, J., and Henry, S.A., 1994, IN02 and IN04 gene products, positive regulators of phospholipid biosynthesis in Saccharomyces cerevisiae, form a complex that binds to the INOl promoter. J. Biol. Chem. 269 15344-15349. 

Cleves, A.E., McGee, T Whitters, E. A., Champion, K.M., Aitken, J.R., Dowhan, W., Goebl, M., and Bankaitis, VA., 1991b, Mutations in the CDP-choline pathway for phospholipid biosynthesis bypass the requirement for an essential phospholipid transfer protein. Cell 64 789-800. 

Volatile fatty acids are by-products in the formation of long-chain fatty acids, which are required for cell membrane phospholipid biosynthesis. The biosynthesis of volatile fatty acids is generally controlled by the same factors that control the formation of ethyl fatty acid esters, that is, oxygen, ergosterol and various insoluble solids (grape solids, clarification solids, yeast hulls) tends to suppress production whereas sugar concentration and clarification are stimulatory (Bardi et al. 1999 Delfini et al. 1992, 1993 Edwards et al. 1990 Houtman et al. 1980). 

Phospholipids — arachidonic acid - Arachidonic acid metabolites appear not to be stored within cells. Their biosynthesis depends upon the appearance of substrate at or near the microsomal synthetase complex(es). According to current thinking, arachidonic acid is stored in the phospholipid fraction of the cell from which the free fatty acid is liberated by the action of a phospholipase... 

Nardone LL, Andrews SB (1979) Cell line A549 as a model of the type II pneumocyte. Phospholipid biosynthesis from native and organometallic precursors. Biochim Biophys Acta 573(2) 276-295... 

Shapiro DL, Nardone LL, Rooney SA et al (1978) Phospholipid biosynthesis and secretion by a cell line (A549) which resembles type II aleveolar epithelial cells. Biochim Biophys Acta 530(2) 197-207... 

Asymmetry. Biological membranes are asymmetric that is, the lipid composition of each half of a bilayer is different. For example, the human red blood cell membrane possesses substantially more phosphatidylcholine and sphingomyelin on its outside surface. Most of the membrane s phosphatidylserine and phos-phatidylethanolamine are on the inner side. Membrane asymmetry is not unexpected, because each side of a membrane is exposed to a different environment. Asymmetry originates during membrane synthesis, because phospholipid biosynthesis occurs on only one side of a membrane (Special Interest Box 12.3). The protein components of membranes (discussed below) also exhibit considerable asymmetry with distinctly different functional domains within membrane and on the cytoplasmic and extracellular faces of membrane. 

Phospholipid biosynthesis at the interface between the endoplasmic reticulum (ER) and the cytosol presents a number of challenges that must be solved by the cell. Explain how each of the following is handled. 

This chapter provides an overview of eukaryotic phospholipid biosynthesis. A discussion of phospholipid synthesis in mammalian cells is emphasized but the synthesis of phospholipids in yeast is also discussed. Phospholipid synthesis in plants is considered in Chapter 4 and in bacteria in Chapter 3. Phospholipids make up the essential milieu of cellular membranes and act as a barrier for entry of compounds into cells. Phospholipids also function as precursors of second messengers such as diacylglycerol (DG) and inositol-1,4,5-P3. A third, and usually overlooked function of phospholipids, is storage of energy in the form of fatty acyl components. This function is probably quantitatively important only under extreme conditions such as starvation. 

F5 40 Phospholipid biosynthesis and cell wall deposition (prop.) Carboj lic add amides (CAA fungiddes) Dimefhomorph, iprovalicarb, mandipropamid Specific for Oomycetes... 

Palmitic acids play an important role in the synthesis of phospholipids which are the key class of lipids for cell membrane, brain and nerves coordination and integrity (Greseth Traktman, 2014). In some prokaryotes, PA is required for the phospholipids to be synthesis which helps them to survive for example, viral phospholipids biosynthesis for survival (Greseth Traktman, 2014). 

In summary, the site of oleate is most likely the endoplasmic reticulum. This organelle contains, in addition, all the enzymes involved in phospholipid biosynthesis. Whether or not a specific polar lipid or an acyl-CoA or an acyl-ACP is directly or indirectly involved for linoleic synthesis remains for further investigations to clarify. There is indirect evidence suggesting that the monogalactosyldiglyceride in the outer envelope of the chloroplast may be involved in the conversion of linoleic acid to linolenic acid. Once linoleic acid and linolenate are formed, these acyl moieties must be transported to their specific sites. In the leaf cell, the principal site of these acids is the chloroplast lamellar membrane. At present, there is no direct evidence for the occurrence of polyunsaturation in these specific membranes or even in chloroplasts themselves (see Table II). Thus these acyl moieties must be presumably transferred directly or indirectly to their final site from their synthesizing site (see Section III for a discussion of transport mechanisms). 

A different developmental trend in fatty acid composition is observed during culture of muscle cells (Table 3). Stearate steadily increases from 2 to 13 days of culture while linoleate decreases. Simultaneously, there is an increase in arachidonic acid. The standard medium used to grow muscle cells in vitro includes horse serum which is rich in linoleate (42 % of total fatty acids) and contains low amounts of arachidonate (5%). Therefore, the changes observed in fatty acids from muscle developed in vitro might be related to enzymes involved in fatty acid biosynthesis or uptake. If horse serum is replaced in the medium by fetal calf serum with a low content of linoleate (5%), this fatty acid is almost totally replaced in cell phospholipids by oleate. The linoleate content of the cells can be replenished by supplementation of the medium with free linoleate (Fig. 3). This shows a remarkable plasticity of cultured muscle cells to modify their fatty acid composition. The in vitro system could... 

Taking into account this localization a study on the enzymic properties of the de novo mechanism for phospholipid biosynthesis both in neuronal and glial cell fractions seems to be of value. As a first step we have used neurons and glia to investigate the activity of phosphorylethanolamine diacyl glycerol phosphotransferase (EC 2.7.8.1), which catalyse the last step in the synthesis of... 

In mammals the introduction of new double bonds into mono- and polyunsaturated fatty acids exclusively occurs in the carboxyl end and is never directed toward the terminal methyl-group. Therefore no transition of fatty acids belonging to the linoleic acid family into those of the linolenic acid type has been observed. This has been shown by means of terminally labeled synthetic polyunsaturated fatty acids (Stoffel 1961, Klenk 1964). The complete enzyme system for polyunsaturated fatty acid synthesis is arranged on the cytoplasmic membranes. In view of the importance of polyunsaturated fatty acids for the structure of glycero-phospholipids, it is interesting to mention the acyl-transferases catalyzing the acylation of the j8-position of lysolecithin, lysophosphatidic acid and L-a-glycero-phosphate. These and other enzymes of phospholipid biosynthesis are located in the cytoplasmic reticulum, which therefore appears to be the main site of lipid synthesis of the cell. 

Vance, J.E., Vance, D.E. (2004) Phospholipid biosynthesis in mammalian cells. Biochem. Cell Biol. 82, 113-128. 

As shown in Table I, there is substantial in vitro evidence that GTP stimulates anabolic processes in cell-free systems ranging from nucleic acid and protein synthesis through nucleic acid function, protein glyco-sylation, assembly, phospholipid biosynthesis, and even cell wall biosynthesis. As summarized in Table I, GTP influences on 12 different anabolic processes have been characterized in cell-free systems. In each case, GTP stimulates the anabolic process involved. 

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