Cytochrome P450 distribution

They are widely distributed across species. Bacteria possess cytochrome P450s, and P450cani (involved in the metabolism of camphor) of Pseudomonas putida is the only P450 isoform whose crystal stmcture has been established. 

Cytochrome P450-type monooxygenase systems, which have a generally low substrate specificity, are widely distributed in the species of fish used for toxicity testing (Funari et al. 1987). 

Wu, M. L., Wu, X. H. Chen, S. C. (2005). Study on tissue distribution difference of cytochrome P450 2C19 in Chinese population Han. Journal of Chinese Pharmaceuticals, 40(3), 215-18. 

Wacher, V. J., Wu, C. Y., Benet, L. Z., Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein implications for drug delivery and activity in cancer chemotherapy, Mol. Carcinogen. 1995, 13, 129-134. 

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... 

They have large volumes of distribution and are largely metabolized through the cytochrome P450 pathways (except ziprasidone). 

Wacher VJ, Wu CY and Benet LZ (1995) Overlapping Substrate Specificities and Tissue Distribution of Cytochrome-P450 3a and P-Glycoprotein—Implications for Drug-Delivery and Activity in Cancer-Chemotherapy. Mol Carcinog 13 pp 129-134. 

Nishimura M, Yaguti H, Yoshitsugu H, Naito S, Satoh T (2003) Tissue distribution of mRNA expression of human cytochrome P450 isoforms assessed by high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi 123(5) 369-375. 

Abdelgadir SE, Roselli CE, Choate JV, Resko JA. 1997. Distribution of aromatase cytochrome P450 messenger ribonucleic acid in adult rhesus monkey brains. Biol Reprod 57 ... 

Bergh AF, Strobel HW. 1996. Anatomical distribution of NADPH-cytochrome P450 reductase and cytochrome P4502D forms in rat brain effects of xenobiotics and sex steroids. Mol Cell Biochem 162 31-41. 

Karlgren M, Backlund M, Johansson I, Oscarson M, Ingelman-Sundberg M. 2004. Characterization and tissue distribution of a novel human cytochrome P450-CYP2U1. Biochem Biophys Res Commun 315 679-685. 

McFadyen MC, Melvin WT, Murray GI. 1998. Regional distribution of individual forms of cytochrome P450 mRNA in normal adult human brain. Biochem Pharmacol 55 825-830. 

Morse DC, Stein AP, Thomas PE, Lowndes HE. 1998. Distribution and induction of cytochrome P450 lAl and 1A2 in rat brain. Toxicol Appl Pharmacol 152 232-239. 

Roselli CE, Resko JA. 2001. Cytochrome P450 aromatase CYP19) in the non-human primate brain distribution, regulation, and functional significance. J Steroid Biochem Mol Biol 79 247-253. 

Sanghera MK, Simpson ER, McPhaul MJ, Kozlowski G, Conley AJ, et al. 1991. Immunocytochemical distribution of aromatase cytochrome P450 in the rat brain using peptide-generated polyclonal antibodies. Endocrinology 129 2834-2844. 

Some specific molecules that are important in protein-drug interactions have been studied extensively, including cytochrome P450 (CYP450), receptors, membrane transporters, and antibodies (see Table 1.6). Databases about these molecules may also contain information about SNP effects, tissue distribution, and interacting substrates. 

Table 10.5 Distribution of Alzheimer s disease (AD)-related genotypes associated with different cytochrome P450 2D6 (CYP2D6) metabolizer types in Alzheimer s disease...

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