Cytochromes P450 brain

The CNS contains much smaller amounts of drug-metabolizing enzymes than does the liver. The concentrations of the main enzymes in the brain, members of the cytochrome P450 (CYP) superfamily, are only 0.25% of concentration in the liver. But the brain enzymes are not uniformly distributed, as they are in the liver they are concentrated in specific brain areas. Theoretical models have explained that drug metabolism in the CNS cannot influence drug distribution in the blood, but there are marked differences in brain tissue levels depending on the presence... 

Mast, N., Norcross, R., Andersson, U. et al. Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain. Biochemistry 42 14284-14292, 2003. 

Methods Used to Study Brain Cytochrome P450... 

Cytochromes P450 with primarily endogenous function in human brain (Amruthesh et al., 1992 Degtyarenko and Fabian, 1996 Nelson, 1998 Chang and Kam, 1999 Omiecinski etal., 1999 Nebertand Russell, 2002 Stoffel-Wagner, 2003)... 

Cytochrome P450 pathways in human brain cholesterol, steroid hormones, vitamin D, and bile... 

In addition to those mentioned already, the number and type of commercially available tools to aid in the identification and analysis of cytochrome P450 in the brain and elsewhere has exploded in recent years. O Table 3-1 collates some of the available materials as of early 2004, and this will undoubtedly expand in the years to come. Several companies now sell cytochrome P450s themselves in several expression formats, purified for example or supplied in membrane preparations along with NADPH reductase. 

Rat brain DT-diaphorase enzyme hypothesized to be cytochrome P450 reductase (Kemp... 

NADPH-cytochrome P450 reductase was purified from rat brain microsomes. 

High NADPH cytochrome P450 reductase activity is found in immature rat brain and neuronal cultures, but very little cytochrome P450, thus NADPH cytochrome P450 reductase may be involved in cytochrome P450 independent pathways (Ghersi-Egea et al., 1993). 

Eight human brain tumors contained DT-diaphorase, NADH cytochrome b5 reductase and NADPH cytochrome P450 reductase as assessed by enzyme activity and WB (Rampling et al., 1994). 

Amyloid peptides induce cytochrome P450 reductase in neuroblastoma cells. IHC shows strong reductase surrounding amyloid deposits of transgenic mice. Reductase expression pattern resembled neuritic and oxidative stress markers, while nontransgenic mice showed none. IHC of brains from Alzheimer s patients showed reductase in the cytoplasm of cortical neurons versus none in controls (Pappolla et al., 2001). 

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