Chlorinated lipids

Nagle DG, Park PU, Paul VJ (1997) Pitiamide A, a New Chlorinated Lipid from a Mixed Marine Cyanobacterial Assemblage. Tetrahedron Lett 38 6969... 

Brine shrimp toxicity guided fractionation of the extracts from two mixed Fijian collections of the cyanobacteria Lyngbya majuscula and Schizothrix sp. led to the isolation of eleven novel chlorinated lipids, taveuniamides A-K 369-379. All of these metabolites showed an intriguing constellation of unsaturation (olefinic and acetylenic bonds) and chlorination at the two termini of a 15-carbon chain. The central carbon atom of the chain (C-8) was substituted in each case with an N-acetate function. Taveuniamides F 374, G 375 and K 379 were the most potent brine shrimp toxins with LD50S between 1.7 - 1.9 mg mL , while taveuniamides A-E 373-377 showed moderate activity LD50 3-5 mg mL. Taveuniamides G 375, 1 377, and J 378 were essentially inactive at a concentration of 10 mg mL. ... 

It can be seen already from the outline of biological activities and effects of oxidized, nitrated, and chlorinated lipids above that these compounds can contrib-nte snbstantially to inflammatory conditions and other pathologies, although they also have some anti-inflammatory and beneficial actions. Unsurprisingly, therefore, they have been shown to play a part in several diseases, and these are considered in greater detail in subsequent chapters on cardiovascular disease (Chapters 14 by Leibundgut et al. and Chapter 15 by Poll et al.), metabolic disorders (Chapter 17 by... 

Ford, D. A. 2010. Lipid oxidation by hypochlorous acid Chlorinated lipids in atherosclerosis and myocardial ischemia, 5, 835-852. 

Spickett, C. M. 2007. Chlorinated lipids and fatty acids An emerging role in pathology. Pharmacol Ther. 115, 400-9. 

Endotoxin treatment of rodents leading to inflammation has been shown to lead to the production of chlorinated lipids. As previously described, Sattler and coworkers showed that endotoxin treatment led to neuroinflammation with concomitant increased levels of both MPO mRNA and 2-chlorohexadecanal in the brain (Ullen et al. 2010). Our studies have also shown that endotoxin leads to chlorinated lipid production in various systems in vivo (Brahmbhatt et al. 2010). In fact, lipopolysaccharide treatment led to elevated 2-chlorohexadecanoic acid levels in the plasma. These studies also delineated the metabolic clearance pathway for 2-chlorohexadecanoic acid, which is mediated by sequential hepatic co-oxidation, P-oxidation from the co-end, and then subsequent excretion of 2-chloroadipic acid in the urine (Figure 4.3). Furthermore, lipopolysaccharide treatment of rats led to not only the elevation of plasma 2-chlorohexadecanoic acid, but also increased excretion of 2-chloroadipic acid in the urine. 

While 2-chlorohexadecanal is produced in both atherosclerotic lesions and infarcted myocardium, it remains to be seen whether this aldehyde gives rise to chlorinated lipid metabolites as well as the putative incorporation of chlorinated aliphatic groups into complex lipids including triglycerides, phospholipids, and cholesteryl esters. Furthermore, these metabolites need to be assessed in experiments designed to demonstrate biological effects of a-chlorofatty aldehyde. 

FIGURE 4.4 Biological targets of chlorinated lipids. Cyclooxygenase-2 (COX-2) endothelial nitric oxide synthase (eNOS) lysophosphatidylcholine (LPC) and nnclear factor kappa-B (NF-kB). 

Nusshold, C., M. Kollroser, H. Kofeler, G. Rechberger, H. Reicher, A. UUen, E. Bemhart et al. 2010. Hypochlorite modification of sphingomyelin generates chlorinated lipid species that induce apoptosis and proteome alterations in dopaminergic PC 12 neurons in vitro. Q adicBiol 48(12) 1588-600. 

Nagle, D.G., Park, P.U., and Paul, V.J. (1997) Pitiamide A, a new chlorinated lipid from a mixed marine cyanobacterial assemblage. Tetrahedron Lett., 38, 6969-6972. 

Tse SYH, Mak IT, Weglicki WB et al. 1990. Chlorinated aliphatic hydrocarbons promote lipid peroxidation in vascular cells. J Toxicol Environ Health 31 217-226. 

Toxic compounds polychlorinated biphenyls, polycyclic aromatic hydrocarbons, organochlorine pesticides, chlorinated pesticides, dioxins, veterinary drug residues, hormone residues, aflatoxins, toxic compounds in shellfish. Compoimds of nutritional significance in foods vitamins, fat, lipids, carbohydrates, protein, energy-calorific value, proximates, dietary fibre, ash. Other compounds hormones in blood serum... 

Liposomes made from pure phosphatidylcholine or containing lipids that are found in the cell membrane complex of wool (e.g. cholesterol) have been used to encapsulate aqueous chlorine solutions in chlorination processes [61,62]. The results showed improvements in... 

It follows from the above that MPO may catalyze the formation of chlorinated products in media containing chloride ions. Recently, Hazen et al. [172] have shown that the same enzyme catalyzes lipid peroxidation and protein nitration in media containing physiologically relevant levels of nitrite ions. It was found that the interaction of activated monocytes with LDL in the presence of nitrite ions resulted in the nitration of apolipoprotein B-100 tyrosine residues and the generation of lipid peroxidation products 9-hydroxy-10,12-octadecadienoate and 9-hydroxy-10,12-octadecadienoic acid. In this case there might be two mechanisms of MPO catalytic activity. At low rates of nitric oxide flux, the process was inhibited by catalase and MPO inhibitors but not SOD, suggesting the MPO initiation. 

Maliwal BP, Guthrie FE. 1982. In vitro uptake and transfer of chlorinated hydrocarbons among human lipoproteins. J Lipid Res 23(3) 474-479. 

J. R. Lakowicz and D. Hogen, Chlorinated hydrocarbon-cell membrane interactions studies by the fluorescence quenching of carbazole-labeled phospholipids Probe synthesis and characterization ofthe quenching methodology, Chem. Phys. Lipids 26, 1 10 (1980). 

A representative gas chromatogram with ECD of the analysis of various polar chlorinated pesticides isolated from cod liver oil [179] is shown in Fig. 13. Determination of the polar chlorinated pesticides in cod liver oil required clean up of the lipid matrix with a dimethylformamide/water/hexane liquid-liquid partitioning procedure followed by isolation using a normal-phase LC procedures, and final analysis by GC-ECD [179]. 

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