Phospholipid, microsomal

Cosme J, Johnson EF. Engineering microsomal cytochrome P450 2C5 to be a soluble, monomeric enzyme. Mutations that alter aggregation, phospholipid dependence of catalysis, and membrane binding. /FtoZ Chem 2000 275 2545-53. 

The mechanisms involved in the establishment of lipid asymmetry are not well understood. The enzymes involved in the synthesis of phospholipids are located on the cytoplasmic side of microsomal membrane vesicles. Translocases (flippases) exist that transfer certain phospholipids (eg, phosphatidylcholine) from the inner to the outer leaflet. Specific proteins that preferentially bind individual phospholipids also appear to be... 

CHOI J H, CHA B K and RHEE s J (1998) Effects of green tea catechin on hepatic microsomal phospholipase A2 activities and changes of hepatic phospholipid species in streptozotocin-induced diabetic rats , JNutr Sci Vitaminol (Tokyo), 44 (5), 673-83. 

SCDs are a family of microsomal Fe-based metalloenzymes. They act on long-chain saturated acyl CoAs and introduce a ds-double bond at the C-9 or C-10 position. For example, SCDs convert stearic acid into oleic acid, and palmitic acid into palmitoleic acid. Monounsaturated FAs constitute a major component of TGs, cholesteryl esters, and phospholipids. The reaction requires molecular 02 and NADH and generates H20 in the process [3,4]. 

Peroxyl radicals are the species that propagate autoxidation of the unsaturated fatty acid residues of phospholipids (50). In addition, peroxyl radicals are intermediates in the metabolism of certain drugs such as phenylbutazone (51). Epoxidation of BP-7,8-dihydrodiol has been detected during lipid peroxidation induced in rat liver microsomes by ascorbate or NADPH and during the peroxidatic oxidation of phenylbutazone (52,53). These findings suggest that peroxyl radical-mediated epoxidation of BP-7,8-dihydrodiol is general and may serve as the prototype for similar epoxidations of other olefins in a variety of biochemical systems. In addition, peroxyl radical-dependent epoxidation of BP-7,8-dihydrodiol exhibits the same stereochemistry as the arachidonic acid-stimulated epoxidation by ram seminal vesicle microsomes. This not only provides additional... 

The effects of flavonoids on in vitro and in vivo lipid peroxidation have been thoroughly studied [123]. Torel et al. [124] found that the inhibitory effects of flavonoids on autoxidation of linoleic acid increased in the order fustin < catechin < quercetin < rutin = luteolin < kaempferol < morin. Robak and Gryglewski [109] determined /50 values for the inhibition of ascorbate-stimulated lipid peroxidation of boiled rat liver microsomes. All the flavonoids studied were very effective inhibitors of lipid peroxidation in model system, with I50 values changing from 1.4 pmol l-1 for myricetin to 71.9 pmol I 1 for rutin. However, as seen below, these /50 values differed significantly from those determined in other in vitro systems. Terao et al. [125] described the protective effect of epicatechin, epicatechin gallate, and quercetin on lipid peroxidation of phospholipid bilayers. 

There have been several reports where plasma protein binding data was used in the prediction of in vivo properties of compounds. Two papers noted that the ability to predict in vivo clearance from in vitro microsome data was greatly improved when a plasma protein binding term was included [64,65]. In another study, binding to phospholipids and human serum albumin was assessed by HPLC retention times (on IAM and HAS columns, respectively) and used to predict volume of distribution [66]. 

Margolis, J.M. and Obach, R.S. (2003) Impact of nonspecific binding to microsomes and phospholipid on the inhibition of cytochrome P4502 D6 implications for relating in vitro inhibition data to in vivo drug interactions. Drug Metabolism and Disposition, 31 (5), 606-611. 

Table 5.2. Double-Exponential and Bimodal Lorentzian Analyses of DPH Fluorescence Decay Lifetimes in Liver Microsomes and Vesicles of Extracted Phospholipids"1 ...

V4. Vessey, D. A., and Zakim, D., Regulation of microsomal enzymes by phospholipids. II. Activation of hepatic uridine diphosphate-glucuronyltransferase. J. Biol. Chem. 246, 4649-4656 (1971). 

Adversely affects phospholipid composition and synthesis in roots and microsomes from seedlings by inhibition of choline phosphotransferase (6)... 

Belver, A. and J.P. Donaire. 1987. Phospholipid metabolism in roots and microsomes of sunflower seedlings inhibition of choline phosphotransferase activity by boron. Phytochem. 26 2923-2921. 

Several studies have evaluated the effects of oral di(2-ethylhexyl) adipate on various aspects of hepatic lipid metabolism. Feeding di(2-ethylhexyl) adipate (2% of diet) to male Wistar rats for seven days resulted in increased hepatic fatty acid-binding protein as well as in increased microsomal stearoyl-CoA desaturation activity (Kawashima et al., 1983a,b). Feeding the compound at this dose for 14 days resulted in increased levels of hepatic phospholipids and a decline in phosphatidyl-choline phosphatidylethanolamine ratio (Yanagita et al., 1987). Feeding di(2-ethyl-hexyl) adipate (2% of diet) to male NZB mice for five days resulted in induction of fatty acid translocase, fatty acid transporter protein and fatty acid binding protein in the liver (Motojima et al., 1998). 

Assembly of chylomicrons The enzymes involved in triacylglycerol, cholesterol, and phospholipid synthesis are located in Ihe smooth ER. Assembly of the apolipoproteins and lipid into chylomicrons requires microsomal triacylglycerol transfer protein (see p. 229), which loads apo B-48 with lipid. This occurs during transition from the ER to the Golgi, where the particles are packaged in secretory vesicles. These fuse with the plasma membrane releasing the lipoproteins, which then enter the lymphatic system and, ultimately, the blood. 

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