Microsomes brain

Voirol P, Jonzier-Perey M, Porchet F, Reymond MJ, Janzer RC, et al. 2000. Cytochrome P-450 activities in human and rat brain microsomes. Brain Res 855 235-243. 

The LC-MS analyses documented in the reviewed literature include both in vivo and in vitro studies. In in vivo studies, conditions represented various biological matrices including plasma, urine, bUe, and feces. In vitro studies, LC-MS analyses were conducted for glucuronides obtained using recombinant UGT, " liver microsomes, brain microsomes, hepatocytes, " and liver slices. In most of the experiments, electrospray ionization-MS (ESI-MS) was the ionization... 

Compounds that affect activities of hepatic microsomal enzymes can antagonize the effects of methyl parathion, presumably by decreasing metabolism of methyl parathion to methyl paraoxon or enhancing degradation to relatively nontoxic metabolites. For example, pretreatment with phenobarbital protected rats from methyl parathion s cholinergic effects (Murphy 1980) and reduced inhibition of acetylcholinesterase activity in the rat brain (Tvede et al. 1989). Phenobarbital pretreatment prevented lethality from methyl parathion in mice compared to saline-pretreated controls (Sultatos 1987). Pretreatment of rats with two other pesticides, chlordecone or mirex, also reduced inhibition of brain acetylcholinesterase activity in rats dosed with methyl parathion (2.5 mg/kg intraperitoneally), while pretreatment with the herbicide linuron decreased acetylcholine brain levels below those found with methyl parathion treatment alone (Tvede et al. 1989). 

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. 

Like other xenobiotics, cannabinoids also undergo extensive metabolism in the human body to increase their hydrophihc properties for a facihtated ehmination. The metaboHsm of A9-THC has been very well investigated. More than 100 metabolites of A9-THC are known [99] and a good overview of the most important human metaboHtes is given in [100]. MetaboHsm takes place mainly in hepatic microsomes, but also in intestines, brain. 

Miller, K.J. Anderholm, D.C. and Ames, M.M. Metabolic activation of the serotonergic neurotoxin para-chloroamphetamine to chemically reactive intermediates by hepatic and brain microsomal preparations. Biochem Pharmacon>5 mi- lA2, 1986. 

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]. 

Desamaud F, Cadas H, Piomelli D. Anandamide amidohydrolase activity in rat brain microsomes. J Biol Chem 1995 270 6030-6035. 

Lang W, Qin C, Lin C, Khanolkar AD, Goutopoulos A, Fan P, Abouzid K, Meng Z, Biegel D, Makriyannis A. Substrate specificity and stereoselectivity of rat brain microsomal anandamide amidohydrolase. J Med Chem 1999 42 896-902. 

In humans, erythrocytes contain an esterase that displays genetic polymorphism [86], This esterase has been called esterase D (ES-D), a name without connection to the above-presented A-, B-, and C-classification. Three carboxylesterases named HU1, HU2, and HU3 have been found in human liver microsomes. Other tissues where esterases have been found include brain, plasma, stomach, small intestine, and colon [79]. 

Aldehyde dehydrogenase (EC 1.2.1.3) catalyzes the oxidation of aldehydes to acids (see Sect. 3.7.2). The enzyme is ubiquitously distributed, but has mainly been characterized in brain and liver, where it is found in the cytoplasm, mitochondria, and microsomes. It is not clear whether its esterase activity has a physiological role or is a surviving activity inherited from an evolutionary thiolesterase precursor. 

Table 8.5 also lists some of the results obtained for the enzymatic hydrolysis of the nicotinates [45a]. Other results not discussed here include hydrolysis by rat liver and rat brain microsomes, cytosol, and mitochondria, as well as binding to and hydrolysis by human serum albumin [45b] [46] [47], The... 

S. K. Yang, K. Liu, F. P. Guengerich, Enantioselective Hydrolysis of Oxazepam 3-Acetate by Esterases in Human and Rat Liver Microsomes and Rat Brain S9 Fraction , Chirality 1990, 2, 150-155. 

CYP51 found in rat brain microsomal fraction (Aoyama et al, 1996a). 

Human CYP46 in brain microsomal fraction by RNA and protein blots (Lund et al,... 

Rat brain microsomes 7-a-hydroxylate DHEA and pregnenolone (Akwa et al., 1992). Mouse brain metabolizes [7a- H] pregnenolone and makes 7a-OH-DHEA (Rose et al., 1997). 

P450db1 Immunobiot shows protein in rat and human brain microsomes (Fonne-Pfister et ai., 1987). 

Quinidine and anti-CVP2D6 antibody inhibit DXM metabolism in rat brain microsomes DXM metabolism shows significant regional variation (Tyndaie et al., 1999). 

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