Fatty acid microsomal

Fig. 1. Relative composition of root microsomal membranes from 24 land races, varieties and breeding lines of rice which differ in their salt resistance. Campesterol, Stigmasterol and Sitosterol as % of total sterols 16 0, 18 1, 18 2 and 18 3 fatty acids as % of total fatty acids Na transport on a relative scale from (1) lowest to (9) highest. Data of D.R. Lachno, T.J. Flowers A.R. Yeo (unpublished).

This pathway (the microsomal system ) elongates saturated and unsaturated fatty acyl-CoAs (from Cjg upward) by two carbons, using malonyl-CoA as acetyl donor and NADPH as reductant, and is catalyzed by the microsomal fatty acid elongase system of enzymes (Figure 21-5). Elongation of stearyl-CoA in brain increases rapidly during myehnation in order to provide C22 and C24 fatty acids for sphingoEpids. 

Figure 21-S. Microsomal elongase system for fatty acid chain elongation. NADH is also used by the reductases, but NADPH is preferred.

Figure 23-3. Biosynthesis of the co9, co6,and co3 families of polyunsaturated fatty acids. Each step is catalyzed by the microsomal chain elongation or desaturase system 1,elongase 2,A desaturase 3,A desaturase 4,A desaturase. ( .Inhibition.)...

FAAH was originally purified and cloned from rat liver microsomes and is able to catalyse the hydrolysis of anandamide and 2-AG, in addition to other long-chain fatty acid amides [25]. Studies into the structure and role of this enzyme have generated interest in the potential therapeutic applications of FAAH inhibitors [26-28]. FAAH knock-out mouse brains contained 15-fold higher levels of anandamide than their wild-type counterparts and these animals have also been shown to be more responsive to exogenously administered anandamide [29]. These animals also showed a reduced response to painful stimuli, supporting the hypothesis that FAAH inhibition may provide novel analgesics. Levels of 2-AG were not elevated in the FAAH knock-out animals, apparently due to the existence of alternative metabolic fates for this compound [30]. 

During catabolic and anabolic processes, a renovation of the molecular cellular components takes place. It should be emphasized that the catabolic and anabolic pathways are independent of each other. Be these pathways coincident and differing in the cycle direction only, the metabolism would have been side-tracked to the so-called useless, or futile, cycles. Such cycles arise in pathology, where a useless turnover of metabolites may occur. To avoid this undesirable contingency, the synthetic and degradative routes in the cell are most commonly separated in space. For example, the oxidation of fatty acids occurs in the mitochondria, while the synthesis thereof proceeds extramitochondrially, in the microsomes. 

Hydrolysis of triacylglycerides in tissues is effected by a tissue enzyme, tri-acylglyceride lipase, which hydrolyzes triacylglycerides to glycerol and free fatty acids. There are a variety of tissue lipases that differ primarily in their optimum pH and their location in the cell. The acidic lipase is contained in lysosomes the basic lipase, in microsomes and the neutral lipase, in cytoplasm. A specific feature of the tissue lipase is its sensitivity to hormones which, by activating adenylate cyclase, elicit the transition of the inactive tissue lipase to its active... 

One of the sex pheromone components of the housefly, Musca domestica, is Z9-21 H that is found on the cuticular surface of the fly. This compound is formed by the elongation of Z9-18 CoA using malonyl-CoA and NADPH to Z15-24 CoA which is decarboxylated to form Z9-21 Hc (Fig. 3) [78-80]. Other pheromone components include an epoxide and ketone that are produced from Z9-21 Hc by a cytochrome P450 [81,82] and methyl-branched alkanes that are produced by the substitution of methylmalonyl-CoA in place of malonyl-CoA at specific points during chain elongation [83,84]. A novel microsomal fatty acid synthase is involved in production of methyl-branched alkanes in most insects [85-87]. This fatty acid synthase is different from the ubiquitous soluble fatty acid synthase that produces saturated straight chain fatty acids in that it is found in the microsomes and prefers methylmalonyl-CoA. The amino acids valine and isoleucine can provide the carbon skeletons for methylmalonyl-CoA as well as propionate [83]. 

Support for this conclusion is provided by the hydroperoxide specificity of BP oxidation. The scheme presented in Figure 6 requires that the same oxidizing agent is generated by reaction of h2°2/ peroxy acids, or alkyl hydroperoxides with the peroxidase. Oxidation of any compound by the iron-oxo intermediates should be supported by any hydroperoxide that is reduced by the peroxidase. This is clearly not the case for oxidation of BP by ram seminal vesicle microsomes as the data in Figure 7 illustrate. Quinone formation is supported by fatty acid hydroperoxides but very poorly or not at all by simple alkyl hydroperoxides or H2C>2. The fact that... 

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... 

Prepare microsomes from borage seeds, lipid extraction, and fatty acid analysis according to Galle et al. (31). Protocol adapted from ref. (31). 

Lu, A.Y. and Coon, M.J. (1968) Role of hemoprotein P-450 in fatty acid omega-hydroxylation in a soluble enzyme system from liver microsomes. Journal of Biological Chemistry, 243 (6), 1331-1332. 

Schoch, G.A., Yano, J.K., Wester, M.R., Griffin, K.J., Stout, C.D. and Johnson, E.F. (2004) Structure of human microsomal cytochrome P450 2 C8. Evidence for a peripheral fatty acid binding site. The Journal of Biological Chemistry, 279, 9497-9503. 

The FAS multi-enzyme complex synthesizes saturated C16 fatty acids, but cells and tissues need unsaturated and longer chain fatty acids. The palmitoyl-CoA can be modified by either chain elongation and/or oxidation in order to produce different fatty acid molecules. Both elongation and desaturation occur within the smooth endoplasmic reticulum (SER, microsomal fraction) of the cell. 

The physiological functions of carboxylesterases are still partly obscure but these enzymes are probably essential, since their genetic codes have been preserved throughout evolution [84] [96], There is some evidence that microsomal carboxylesterases play an important role in lipid metabolism in the endoplasmic reticulum. Indeed, they are able to hydrolyze acylcamitines, pal-mitoyl-CoA, and mono- and diacylglycerols [74a] [77] [97]. It has been speculated that these hydrolytic activities may facilitate the transfer of fatty acids across the endoplasmic reticulum and/or prevent the accumulation of mem-branolytic natural detergents such as carnitine esters and lysophospholipids. Plasma esterases are possibly also involved in fat absorption. In the rat, an increase in dietary fats was associated with a pronounced increase in the activity of ESI. In the mouse, the infusion of lipids into the duodenum decreased ESI levels in both lymph and serum, whereas an increase in ES2 levels was observed. In the lymph, the levels of ES2 paralleled triglyceride concentrations [92] [98],... 

B. S. Kaphalia, R. R. Fritz, G. A. S. Ansari, Purification and Characterization of Rat Liver Microsomal Fatty Acid Ethyl and 2-Chloroethyl Ester Synthase and Their Relationship with Carboxylesterase (p/ 6.1) , Chem. Res. Toxicol. 1997, 10, 211 -218. 

Polyunsaturated fatty acids in general and arachidonic acid in particular are especially of interest. With its four C=C bonds, arachidonic acid (10.51) can be oxidized by cytochrome P450 to four regioisomeric monoepoxides, namely the epoxyeicosatrienoic acids (EETs). The four epoxides, although chemically stable, were shown to be hydrolyzed to the corresponding vicinal diols by mouse liver cytosolic EH but not by microsomal EH... 

Moody DE, James JL, Smuckler EA. 1990. Phenobarbital pretreatment alters the localization of CCF -induced changes in rat liver microsomal fatty acids. Toxicol AppI Pharmacol 103 16-27. 

CN197 Eder, K., and M. Kirchgessner. Activities of liver microsomal fatty acid desaturases in zinc-deficient rats force-fed diets with a coconut oil/safflower oil mixture of linseed oil. Biol Trace Elem Res 1995 48(3) 215-229. 

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