Cytochrome brain tissue

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... 

Farin EM, Omiecinski CJ. 1993. Regiospecific expression of cytochrome P-450s and microsomal epoxide hydrolase in human brain tissue. J Toxicol Environ Health 40 317-335. 

The relatively high affinity of these chemicals for lipid-rich tissues (Lipniak and Brandys, 1993) leads to disposition of B(a)P in rodent brain regions (Das et al, 1985). The intra-regional distribution of cytochrome P450 in brain tissues contributes to quantitative differences in PAH metabolite levels (Saunders et al, 2002 Brown et al, 2007). Several... 

The metabolic pathways leading to the production of these urinary pyridinium metabolites are likely to be mediated by one or more forms of liver cytochrome P450. In vitro metabolic studies with rodent (Igarashi et al., unpublished results) and human (Usuki et al., submitted) microsomal preparations have demonstrated the NADPH-dependent oxidation of both HP and HPTP to HPP. Ongoing studies in the authors laboratory have shown that HPP and related pyridinium metabolites are present in brain tissues obtained from C57 black mice that had been treated with HPTP (Van der Schyf et al. 1994). Additionally, results obtained from intra-cerebral microdialysis, mitochondrial respiration, and rat embryonic mesencephalic cell culture studies suggest that HPP possesses MPP type neurotoxic properties (Rollema et al. 1992, 1994 Bloomquist et al. 1994). 

L-Tyrosine metabohsm and catecholamine biosynthesis occur largely in the brain, central nervous tissue, and endocrine system, which have large pools of L-ascorbic acid (128). Catecholamine, a neurotransmitter, is the precursor in the formation of dopamine, which is converted to noradrenaline and adrenaline. The precise role of ascorbic acid has not been completely understood. Ascorbic acid has important biochemical functions with various hydroxylase enzymes in steroid, dmg, andhpid metabohsm. The cytochrome P-450 oxidase catalyzes the conversion of cholesterol to bUe acids and the detoxification process of aromatic dmgs and other xenobiotics, eg, carcinogens, poUutants, and pesticides, in the body (129). The effects of L-ascorbic acid on histamine metabohsm related to scurvy and anaphylactic shock have been investigated (130). Another ceUular reaction involving ascorbic acid is the conversion of folate to tetrahydrofolate. Ascorbic acid has many biochemical functions which affect the immune system of the body (131). 

Hydrogen sulfide inhibits mitochondrial cytochrome oxidase, resulting in disruption of the electron transport chain and impairing oxidative metabolism. Nervous and cardiac tissues, which have the highest oxygen demand (e.g., brain and heart), are especially sensitive to disruption of oxidative metabolism (Ammann 1986 Hall 1996). 

Cholesterol transport and regulation in the central nervous system is distinct from that of peripheral tissues. Blood-borne cholesterol is excluded from the CNS by the blood-brain barrier. Neurons express a form of cytochrome P-450, 46A, that oxidizes cholesterol to 24(S)-hydroxycholesterol [11] and may oxidize it further to 24,25 and 24,27-dihydroxy products [12]. In other tissues hydroxylation of the alkyl side chain of cholesterol at C22 or C27 is known to produce products that diffuse out of cells into the plasma circulation. Although the rate of cholesterol turnover in mature brain is relatively low, 24-hydroxylation may be a principal efflux path to the liver because it is not further oxidized in the CNS [10]. 

Adults require 1-2 mg of copper per day, and eliminate excess copper in bile and feces. Most plasma copper is present in ceruloplasmin. In Wilson s disease, the diminished availability of ceruloplasmin interferes with the function of enzymes that rely on ceruloplasmin as a copper donor (e.g. cytochrome oxidase, tyrosinase and superoxide dismutase). In addition, loss of copper-binding capacity in the serum leads to copper deposition in liver, brain and other organs, resulting in tissue damage. The mechanisms of toxicity are not fully understood, but may involve the formation of hydroxyl radicals via the Fenton reaction, which, in turn initiates a cascade of cellular cytotoxic events, including mitochondrial dysfunction, lipid peroxidation, disruption of calcium ion homeostasis, and cell death. 

Drinking water, 1000 mg KCN/L, exposure for 40 days Marked inhibition of cytochrome oxidase activity in liver, brain, and blood increased cyanide concentrations in all tissues inhibition of rhodanese activity diminished labile sulfur tissue levels 43... 

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