Microsomes, enzymatic lipid

Musgrave ME, Gould SP, Ablett RF (1987) Enzymatic lipid peroxidation in the gonadal and hepatopancreatic microsomal fraction of cultivated mussels Mytilus edulis L.). J Food Sci 52 609-612... 

This mechanism is now considered to be of importance for the protection of LDL against oxidation stress, Chapter 25.) The antioxidant effect of ubiquinones on lipid peroxidation was first shown in 1980 [237]. In 1987 Solaini et al. [238] showed that the depletion of beef heart mitochondria from ubiquinone enhanced the iron adriamycin-initiated lipid peroxidation whereas the reincorporation of ubiquinone in mitochondria depressed lipid peroxidation. It was concluded that ubiquinone is able to protect mitochondria against the prooxidant effect of adriamycin. Inhibition of in vitro and in vivo liposomal, microsomal, and mitochondrial lipid peroxidation has also been shown in studies by Beyer [239] and Frei et al. [240]. Later on, it was suggested that ubihydroquinones inhibit lipid peroxidation only in cooperation with vitamin E [241]. However, simultaneous presence of ubihydroquinone and vitamin E apparently is not always necessary [242], although the synergistic interaction of these antioxidants may take place (see below). It has been shown that the enzymatic reduction of ubiquinones to ubihydroquinones is catalyzed by NADH-dependent plasma membrane reductase and NADPH-dependent cytosolic ubiquinone reductase [243,244]. 

Antioxidant activity was also tested in a liver microsome system. In this study, mice were treated by oral intubation (2 times/wk) with 0.2 ml olive oil alone or containing CLA (0.1 ml), linoleic acid (0.1 ml), or dl-a-tocopherol (lOmg). Four weeks after the first treatment, liver microsomes were prepared and subsequently subjected to oxidative stress using a non-enzymatic iron-dependent lipid peroxidation system. Microsomal lipid peroxidation was measured as thiobarbituric acid-reactive substance (TBARS) production using malondialdehyde as the standard. It was found that pretreatment of mice with CLA or dl-a-tocopherol significantly decreased TBARS formation in mouse liver microsomes (p < 0.05) (Sword, J. T. and M. W. Pariza, University of Wisconsin, unpublished data). 

There are other cases of inhibition of lipid enzymatic pathways by trans fatty acid isomers. The above reported mono-14 -trans isomer of arachidonic acid is inhibitor of the synthesis of thromboxane B2 and, therefore, can prevent rat platelet aggregation [52]. The transformation of mono-trans isomers of linoleic acid by rat liver microsomes showed that the 9-cis,12-trans isomer is better desaturated, whereas the 9-trans, 2-cis isomer (Scheme 6.1) is better elongated [53]. 

THC and CBD differ in their action on membrane electrical properties. It has also been found that THC causes large shifts in the transition temperature of membrane lipids [ 110, 111 ]. A possible relationship between this effect and microsomal demethylase activity was observed, and it was suggested that THC could influence enzymatic action by membrane effects. 

Oxidative cleavage of the O-alkyl linkage in glycerolipids is catalyzed by a microsomal tetrahydropteridine (Pte-H4)-dependent alkyl monooxygenase (Fig. 12) (T.-C. Lee, 1981). The required cofactor, Pte H4, is regenerated from Pte-Hj by an NADPH-linked pteridine reductase, a cytosolic enzyme. Oxidative attack on the ether bond in lipids is similar to the enzymatic mechanism described for the hydroxylation of phenylalanine. Fatty aldehydes produced via the cleavage reaction can be either oxidized to the corresponding acid or reduced to the alcohol by appropriate enzymes. 

It is well established that liver microsomes in the presence of NADPH and in the absence of chelator are capable of oxidizing cholesterol and other 3P-hydroxy 5-unsaturated steroids yielding the common autoxidation products 3-8 [16]. In this case, the cholesterol oxidation is secondary to the enzymatic NADPH-dependent lipid peroxidations. The enzyme-catalyzed reaction is required, however, merely to reduce Fe i to Fe which in turn catalyzes ordinary autoxidation. It has also been shown by EPR studies using spin traps that radicals are involved in these conversions [16]. The major radicals detected were lipid peroxyl radicals and superoxide, whereas only small amounts of hydroxyl radicals were... 

Most xenobiotics are biotransformed by enzymes in the liver, although there is also significant xenobiotic enzyme activity elsewhere in the body. These hepatic enzymes have broad specificity and can metabolize a wide variety of xenobiotics. Within the fiver the biotransforming enzymes are located in the microsomes (smooth endoplasmic reticulum), due to the solubility of fipophific xenobiotics in lipid membranes. There is also additional enzymatic activity in the cytosol and to a smaller extent in other areas of the cell. 

Lipid oxidation in subcellular fractions can be mediated by enzyme systems in muscle microsomes that maintain iron in the ferrous form by reduced nicotinamide adenine dinucleotide (NADH). However, this redox system may not be enzymatic because, unlike lipoxygenase, no specific lipid oxidation products have been identified. Ascorbate and other reducing agents may have the same effects in the presence of heme-protein complexes. On the other hand, the presence of 15-lipoxygenase in chicken muscle may be responsible for oxidative deteriorations in uncooked chicken meat during frozen storage. Phospholipases... 

---