Phosphatidylcholines oxidation reactions

The mechanism in hepatic cellular metabolism involves an electron transport system that functions for many drugs and chemical substances. These reactions include O-demethylation, N-demethyla-tion, hydroxylation, nitro reduction and other classical biotransformations. The electron transport system contains the heme protein, cytochrome P-450 that is reduced by NADPH via a flavoprotein, cytochrome P-450 reductase. For oxidative metabolic reactions, cytochrome P-450, in its reduced state (Fe 2), incorporates one atom of oxygen into the drug substrate and another into water. Many metabolic reductive reactions also utilize this system. In addition, there is a lipid component, phosphatidylcholine, which is associated with the electron transport and is an obligatory requirement for... 

Many references to kinetic measurements may have already been covered earlier with other physical methods. These include studies on pseudorotation of stereoisomers of a 10-P-5 spirophosphorane, on the formation rate of acylpho-sphonate hemiketals, on the rate of decomposition of hydroperoxides formed by the oxidation of soya phosphatidylcholine, on the kinetics of the reaction of trimethyl phosphite with benzylidene acetophenones, calorimetric studies on the reaction kinetics of dithiophosphoric acid 0,0 -dialkyl esters with zinc oxide, " and the kinetics of selective dephosphorylation of 2 -phosphorylated and 2 -thiophosphorylated dinucleotides. 

Those include C-, N- and 5-oxidations, N-, 0- and 5-deaIkylation, deaminations, and certain dehalogenations. Under anaerobic conditions, it can also catalyze reductive reactions. The CYP monooxygenase system is a multien-zymatic complex constituted by the CYP hemoprotein, the flavoprotein enzyme NADPH CYP reductase, and the unsatnrated phospholipid phosphatidylcholine. The isoforms involved in xenobiotic metabolism are membrane bonnd enzymes situated in the endoplasmic reticnlnm. After... 

A simple method to measure the membrane permeability to specific molecules has been presented by G. Battaglia and coworkers [141], The authors encapsulated highly hydrophilic 3,3, 3//-phosphinidynetris-benzenesulfonic acid (PH) into polyethylene oxidc)-co-poly(butylene oxide) (EB) vesicles and monitored its reaction with 5,5/-dithiobis-2-nitrobenzoic acid (DTNB) penetrating the membrane from the exterior. The reaction rate (amount of the formed product as a function of time after DTNB addition) measured with IJV/Vis was directly correlated to the permeability of the permeating molecule. A comparison of these results with the permeability of egg yolk phosphatidylcholine (PC) vesicles showed that EB membranes have a more selective permeability toward polar molecules than the phospholipids membranes. Also in this case the permeability appeared to depend on the membrane thickness as predicted by Fick s first law. 

Phospholipids contribute specific aroma to heated milk, meat and other cooked foods through lipid oxidation derived volatile compounds and interaction with Maillard reaction products. Most of the aroma significant volatiles from soybean lecithin are derived from lipid decomposition and Maillard reaction products including short-chain fatty acids, 2-heptanone, hexanal, and short-chain branched aldehydes formed by Strecker degradation (reactions of a-dicarbonyl compounds with amino acids). The most odor-active volatiles identified from aqueous dispersions of phosphatidylcholine and phos-phatidylethanolamine include fra 5 -4,5-epoxy-c/5-2-decenal, fran5,fran5-2,4-decadienal, hexanal, fra 5, d5, d5 -2,4,7-tridecatrienal (Table 11.9). Upon heating, these phospholipids produced cis- and franj-2-decenal and fra 5-2-undecenal. Besides fatty acid composition, other unknown factors apparently affect the formation of carbonyl compounds from heated phospholipids. 

Five different steps have been distinguished in the hydroxylation reaction (1) combination of the substrate (RH) with the oxidized form of cytochrome P450, (2) reduction of the ferric state of the cytochrome s iron atom to the ferrous state by the transfer of one electron from NADPH through the catalytic action of the reductase (the reaction requires phosphatidylcholine), (3) formation of a ternary complex through the binding of oxygen, (4) formation of a superoxide anion bound to the oxidized cytochrome P450 after an intramolecular electron transfer, and (5) finally in the molecular complex (oxidized cytochrome, superoxide, and substrate), the superoxide attacks the substrate which becomes hydroxylated, and at the same time the reductase provides another electron and a molecule of water is formed as one of the products of the reaction. 

Nakanishi, H., lida, Y., Shimizu, T. and Taguchi, R. (2009) Analysis of oxidized phosphatidylcholines as markers for oxidative stress, using multiple reaction monitoring with theoretically expanded data sets with reversed-phase liquid chromatography/tandem mass spectrometry. J. Chromatogr. B 877, 1366-1374. 

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