Oxidation susceptibility

The extent of membrane lipid polyunsaturation is another modulator of cellular oxidative susceptibility an example is mentioned above in the NO section. This is not surprising, and it has a chemical rationale since the sites of attack of oxidizing free radical species in lipids are the double bonds in polyunsaturated phospholipid stmctures in membranes. Therefore, it follows. 

Fatty acid modification changes oxidative susceptibility... 

Mathur, S., Devaraj, S., Grundy, S.M., and Jialal, L, Cocoa products decrease low density lipoprotein oxidative susceptibility but do not affect biomarkers of inflammation in humans, J. Nutr., 132, 3663, 2002. 

Nonspecific cytochrome P450-mediated oxidation involves enzyme-catalyzed formation of reactive oxygen species (superoxide anions and hydroxyl radicals), which oxidize susceptible amino acids such as proline, arginine, lysine, and histidine. 

The chemical properties of organosulfur, organoselenium, and organotellnrinm compounds are markedly similar. Because bond stability with carbon decreases with the increasing atomic number of the element, thermal stability decreases, whereas oxidation susceptibility increases to such an extent that alkyl tellurides are oxidized rapidly by air at room temperature. As a result, less has been written concerning the chemistry of organotellurium than organoselenium compounds. Nevertheless, a sizable literature exists (29,55—59). 

The drug designer must consider the susceptibility to, and consequences of, the principal Phase 1 metabolic reactions hydrolysis, reduction and oxidation. Susceptibility to oxidation can be calculated using semi-empirical molecular orbital theory. Ease of oxidation is reflected by the energy of the HOMO, and the probable site of oxidation can be predicted from calculation of the electrophilic superdelocalizability. Likewise, ease of reduction is related to LUMO energy, and probable site to nucleophilic superdelocalizability (Loew and Burt, 1990). 

Pijanowski, E., Wojtowicz, M. and Lochowska, H. 1962. On the oxidative susceptibility of milk from cows of different yields. Int. Dairy Congr. A, 633-640. 

Wan Y, Vinson JA, Etherton TD, Proch J, Lazarus SA, Kris-Etherton PM. 2001. Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans. Am J Clin Nutr 74 596-602. 

A quantitative expression of the oxidative susceptibility can give an idea of the degree of protection the molecule will require in formulations. Some authors proposed kinetic methods for the quantitative evaluation of the sensitivity of a molecule to hydroxy and peroxy radicals (62). 

Rebole, A., Rodriguez, M.L., Ortiz, L.T., Alzueta, C., Centeno, C., Viveros, A., Brenes, A. and Arija, I. (2006) Effect of dietary high-oleic acid sunflower seed, palm oil and vitamin E supplementation on broiler performance, fatty acid composition and oxidation susceptibility of meat. British Poultry Science 47, 581-591. 

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