New Lipids

New Lipids.—Studies, mainly by Mikolajczak and Smith,have unravelled the structures of the unusual alcohols in the cyano-lipids (13—55%) which accompany the more conventional triglycerides in several sapindaceous seed oils and in one borage. The branched-chain Cg cyano-alcohols (12)—(15) occur as mono- or di-acyl derivatives 

Most phospholipids contain glycerol, phosphoric acid, a short-chain hydroxy-compound, and long-chain acids or alcohols. Minor variants of this pattern and new ways of associating these components continue to be identified, as for example the phosphatidyl-AT-(2-hydroxyethyl)alanine (16) from rumen protozoa.  

The so-called triglycerides of starfish contain 35% of the monoacyl monoalkyl (or monoalk-l -enyl) derivatives of ethanediol. It is considered that the fatty tissues in the melon and jaw oils of dolphins, porpoises, and toothed whales may play a major role in the echolocation system of these animals. Litchfield et al. have examined the melon oil and blubber of the Beluga whales, and report that the former remains clear at temperatures well below 0 °C, a property which is related to its unusual triglyceride composition. 

When glycerol 1-phosphorylcholine is treated with an acyl halide, the expected phosphatidylcholine is accompanied by cyclic lysolecithin,  

The chemistry of the sulpholipids has been reviewed (see ref. 152/). The major sulpholipid from Ochromonas danica is a hexachloro-C22 disulphate (19).3  

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The new lipid occurred only in the plasma hpids of newborns and was not present in membrane hpids of red cell membranes or platelets. Total lipids were extracted from plasma and from red blood cell membranes and platelets. A total lipid profile was obtained by a three-directional PLC using silica gel plates and was developed consecutively in the following solvent mixtures (1) chloroform-methanol-concen-trated ammonium hydroxide (65 25 5, v/v), (2) chloroform-acetone-methanol-ace-tic acid-water (50 20 10 15 5, v/v), and (3) hexane-diethyl ether-acetic acid (80 20 1, v/v). Each spot was scraped off the plate a known amount of methyl heptadecanoate was added, followed by methylation and analysis by GC/MS. The accmate characterization of the new lipid was realized using NMR technique. 

Figure 17.2 Lipid peroxidation scheme. LH, a polyunsaturated fatty acid LOOM, lipid hydroperoxide LOH, lipid alcohol L, lipid radical LOO, lipid hydroperoxyl radical LO, lipid alkoxyl radical. Initiation the LH hydrogen is abstracted by reactive oxygen (e.g. lipid alkyl radical, lipid alkoxy radical, lipid hydroperoxyl radical, hydroxy radical, etc.) to produce a new lipid alkyl radical, L. Propagation the lipid alkyl, alkoxyl or hydroperoxyl radical abstracts hydrogen from the neighbouring LH to generate a new L radical.

D1 (10,17S-docosatriene) from DHA using tandem liquid chromatography-photodiode array-electrospray ionization-tandem mass spectrometry (LC-PDA-ESI-MS-MS)-based lipidomic analysis have been documented in ischemic brain [4] and retinal pigment epithelium [5], This new lipid is called neuroprotectin D1 (1) because of its neuro-protectiveproperties in brain ischemia-reperfusion [4] and in oxidative stress-challenged retinal pigment epithelial cells [5] (2) because of its potent ability to inactivate proapoptotic signaling (see apoptosis, Ch. 35) [5] and (3) because it is the first identified neuroprotective mediator derived from DHA. 

Larabi M, et al. New lipid formulation of amphotericin B spectral and microscopic analysis. Biochim Biophys Acta 2004 1664 172. 

Larabi M, et al. Study of the toxicity of a new lipid complex formulation of amphotericin B. J Antimicrob Chemother 2003 53 81. 

Ivancev I, Lunderquist A, Hochbergs P, Wretlind A (1989) Clinical trials with a new lipid emulsion for computed tomography of the liver. Acta Radiol 30 449... 

Caillot, D., Chavanet, P, Casasnovas, O., Solary, E., Zanetta, G., Buisson, M., Wagner, O., Cuisenier, B., Bonnin, A., Camerlynck, P, et al. (1992) Clinical evaluation of a new lipid-based delivery system for intravenous administration of amphotericinEUr. J. Clin. Microbiol. Infect. Dis., 11 722-725. 

The physicochemical characterization of complexes formed between plasmid DNA and products 2 and 3 demonstrates a different behaviour of the new lipid/ DNA complexes, compared to previously described cationic lipids that classically compact DNA and retard DNA in gel electrophoresis. The different nature of the complexes, and especially the unperturbed electrophoretical mobility we have observed, propose them as potential self-assembling systems for gene delivery (Scherman et al., 2001). 

Caracciolo G, Pozzi D, Caminiti R et al (2003) Structural characterization of a new lipid/DNA complex showing a selective transfection efficiency in ovarian cancer cells. Eur Phys J E 10 331-336... 

ABSTRACT The Myxomycetes (true slime molds) are an unusual group of primitive organisms that may be assigned to one of the lowest classes of eukaryotes. As their fruit bodies are very small and it is very difficult to collect much quantity of slime molds, few studies have been made on the chemistry of myxomycetes. Cultivation of the plasmodium of myxomycetes in a practical scale for natural products chemistry studies is known only for very limited species such as Physarum polyeephalum. We recently studied the laboratory-cultivation of myxomycetes and several species have been successfully cultured in agar plates. Chemical constituents of cultured plasmodia of several species of myxomycetes of the genera Didymium and Physarum were examined to obtain several sterols, new lipid, or pyrroloiminoquinone derivatives. Previous studies on the chemistry of the secondary metabolites of myxomycetes by other groups are also described here. 

The isolation of lipids from cells or tissues is not as simple and straightforward as one might desire, but is essentially an important adjunct to characterization of membranes (composition, lipid-to-protein ratio, structure proof, definition, new lipids, etc.). While this is recognized by many investigators in the field, it is difficult for the novice in this area to become aware of some of the potential problems in extraction procedures and the reasons for particular approaches. Thus it seems fitting at this point in time to comment on some of the nuances of the approaches used in isolation, purification, and identification of lipids present in cell membranes. These topics are subdivided into areas which are considered to be of major import to a successful consideration of the extraction procedure. 

Reports describing the design of new lipid architectures continue to appear in the literature. A few instances of case studies involving newer approaches toward lipid design for achieving control of membrane level properties will be discussed in the present section. 

Therefore a detailed study of the influence of dimerization of well-defined synthetic lipids seems to be the most direct approach to achieve an understanding of the role of these complex amphiphilic molecules in living cells. In addition, new lipidic materials based on dimerization might be of practical value. Based on these expectations, several reports describing the design, synthesis and characterization of a number of new dimeric lipids have appeared in recent literature. Most of these lipids are made up of two identical monomeric lipid moieties connected at the level of the head groups or very close to these by a spacer unit, which can be either hydrophilic or hydrophobic, or even be either rigid or flexible. 

Biotechnological transformation is powerful tool to effectively utilize a broad variety of plant oils, with the aim to modify their structure for the production of new lipid-based materials with demanded properties and functions. One method of plant oil transformation is based on the direct utilization by microorganisms. Employed oils can be converted to aimed compounds by submerged cultivation or oils, and/or oleaginous plant materials can be utilized during solid state fermentation to useful bioproducts enriched with demanded microbial products. Another biotransformation technique covers the enzymatic modification of oil components to structured lipids with biological properties. 

Freund, O. (2001), Biodistribution and gastrointestinal drug delivery of new lipidic multilamellar vesicles, Drug Deliv., 8,239-244. 

Jumaa, M., Furkert, F. H., and Muller, B. W. (2002), A new lipid emulsion formulation with high antimicrobial efficacy using chitosan, Eur. J. Pharm. Biopharm., 53,115-123. 

A new lipid constituent methyl-11,12,15-trihydroxy-13(14)-octadecanoate (91) was recently isolated from the leaves of A. annua. A lipophUic fraction of A. annua was found to contain aurantiamide acetate, a dipeptide (92) (Stmcture 5-7). ... 

The commercial introduction of a new lipid source is not a trivial matter. Unless the oil has some specific and novel property (like oils containing y-linolenic acid, for example), it will have to compete with existing oils available in bulk at commodity prices. This exerts a number of constraints. 

Peroxyl radical is reactive to attack another PUFA acyls, abstracting hydrogen. In this reaction lipid hydroperoxide (LOOH) is formed and a new lipid alkil radical is generated [1,2] ... 

Zarif, L. Graybill, D. Berlin, R. Mannino, R.J. Cochleates new lipid-based drug delivery system. J. Liposome Res. 2000,10 (4), 523-538. 

It has been stated that large numbers of mature women are volunteering for the new lipid, heart risk, osteoporosis and arthritis phase 3 studies, due to their concern that women have been represented so poorly as subjects in the past. Phase I studies are of short duration (one to two weeks) but usually require confinement of the volunteers. Because of this time commitment, far fewer mature women volunteer, due to career conflicts or because they are often burdened unequally with family management. Those that do volunteer are generally unattached young female students. Thus, most female volunteers may not be typical of a representative , mature, childbearing population (if this can ever be defined). 

Lipid-based carriers have been established to transport DNA into cells, but the efficiency of protein delivery based on conventional liposomal formulations is below 5%. Zelphati et al., however, have developed a new lipid formulation that interacts rapidly and noncovalently with protein, creating a protective vehicle for delivery.56 The protein encapsulated in the formulation binds to the negatively charged membrane, is internalized in endosomal vesicles by endocytosis, and is then released inside the cell. The system displays no significant toxicity under optimal conditions. 

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