Fatty acids conjugation

Miller-Larsson A, Mattsson H, Hjertberg E, Dahlback M, Tunek A, Brattsand R (1998) Reversible fatty acid conjugation of budesonide. Novel mechanism for prolonged retention of topically applied steroid in airway tissue. Drug Metab Dispos 26(7) 623-630. 

Hasegawa, H., Suzuki, R., Nagaoka, T., Tezuka, Y., Kadota, S., and Saiki, I. (2002). Prevention of growth and metastasis of murine melanoma through enhanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatriol. Biol. Pharm. Bull. 25, 861-866. 

Plant In plants, butylate is metabolized to carbon dioxide, diisobutylamine, fatty acids, conjugates of amines, and other compounds (Hartley and Kidd, 1987 Humburg et al., 1989). 

Antibacterial diterpenes and their fatty acid conjugates from rice leaves. Phytochemistry 2004 65(9) 1291-1298. 

E. Wieslander, E. L. Delander, L. Jarkelid, E. Hjertberg, A. Tunek, and R. Brattsand, Pharmacologic importance of the reversible fatty acid conjugation of budesonide studied in a rat cell line in vitro, Am. J. Respir. Cell. Mol. Biol. 19 477 (1998). 

The pharmacologically active hydroxy metabolites, present either as free or as fatty acid conjugates, will be of prime interest. Sufficient milk volume must be collected to allow HPLC isolation of suspected cannabinoids and off-line mass spectral characterization. 

Although the marine animals have been exploited thoroughly for food and other byproducts, their plant counter parts have not been exploited for food to the same extent, barring some seaweeds like Porphyra (nori) and Laminaria (konbu). Unlike terrestrial counter parts, marine plants have not been looked upon as important substrates for further processing of their lipids. In this section, seaweed lipids have been classified for convenience into different categories, viz., general fatty acids, conjugated fatty acids, carotenoids (fuco-xanthin), and sterols (fucosterol). 

Plant oils are excellent sources of some valuable compounds such as unsaturated fatty acids, phytosterols, squalene, pigments, antioxidants, vitamins, waxes, glycolipids, and lipoproteins. Plant oils could be employed for technological uses as biodiesel, lubricants, surfactants, emulsifiers, biopolymers, and so on. Vegetable oils also can serve as appropriate sources for the production of valuable compounds having applications in food, pharmaceutical, medical, and environmental fields. Attention has been focused on various types of value-added fatty acids (polyunsaturated fatty acids, conjugated fatty... 

The mechanism by which xenobiotic alcohols or esters are converted to fatty acid esters has not been studied. They could be formed by the action of lyase enzymes in the presence of fatty acid glyceryl esters, as in the conversion of farnesol to farnesol fatty acid esters (150). Some lipolytic acyl hydrolase enzymes from plants readily catalyze the transfer of lipid-bound fatty acids to low MW alcohol acceptors (150.151) and enzymes of this class could be responsible for the occasional formation of fatty acid conjugates of xenobiotic alcohols. Mechanisms involving fatty acid acyl CoA, phospholipids, or direct esterification with fatty acids might also be involved (1 ). 

In 1980, another in vivo conjugation of fatty acids to a hydroxylated toxin was identified. Palmitic, stearic, oleic, and linoleic fatty acid conjugates of a 2,2-bls( -chlorophenyl)-ethanol metabolite (DDOH) were isolated from the livers and spleens of DDT-treated male and female rats ( ). 

OH-A -THC were incubatedin an in vitro rat liver microsomal NADPH-generating system ( ). Despite the low yield, the presence of the fatty acid-conjugated cannabinoids in the incubation mixture led our laboratory to assume that this commonly used microsomal mixed function oxidase system was involved in the conjugating process. Soon, however, it was confirmed that an energy-dependent... 

The ll-palm-A -THC can be hydrolyzed to II-OH-A -thc by cholesterol esterase and triacylglycerol lipase but not by phospholipase A, acetylesterase or phosphotransacetylase (16). An attempt to modify the retention of fatty acid-conjugated DDT metabolites was carried out by injecting the DDT-treated rats with sodium salt of various bile acids, heparin or lecithin of which all were known to affect the esterification or ester hydrolysis by the cholesterol esterase system. The results Indicated a significant decrease in the retention of the conjugated DDT metabolites in the rat liver and spleen (17). 

The possibility of nonenzymatic esterification of free fatty acid by the hydroxylated metabolite was ruled out by two experiments (a) hydroxylated metabolites were Incubated with washed microsomes with no added cofactors, and (b) hydroxylated metabolites were Incubated with different concentrations of fatty acid in buffer without microsomes. In both cases, no detectable fatty acid conjugated metabolites were found by TLC analyses ( 6). 

Other Fatty Acid Conjugates Produced by the In Vitro System. 

The results of these in vitro studies demonstrate that conjugation of fatty acids can occur not only with a hydroxyl functional group but also with an amine group. In addition, the isolation of the in vivo fatty acid-conjugated metabolites of DDT, cannablnol and A -THC and A -THC further supports that the in vitro CoA-forti-fled liver microsomal system could be used as an assay method to predict whether certain compounds, or their metabolites, are retained in vivo in llpld-contalning tissues as fatty acid conjugates. 

Postscript A fatty acid-conjugated pesticide palmitoyl pentachlorophenol was Isolated from human fat and reported In the literature after this manuscript was presented at the 189th National ACS Meeting (31). 

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