High impact information on Cyp2d9

• In this study we demonstrated that recombinant rat cytochrome P450 2D1 and 2D4 and human cytochrome P450 2D6 possess progesterone 6 beta- and 16 alpha- hydroxylation activities; 2 beta- and 21-hydroxylation activities; and 2 beta-, 6 beta-, 16 alpha- and 21-hydroxylation activities, respectively [1].
• Regional distribution of cytochrome P450 2D1 in the rat central nervous system [2].
• Isolated hepatocytes were also prepared from Dark Agouti (DA) rats deficient in CYP2D1, and were incubated with EM or CD [3].
• In conclusion all findings indicated that the enzyme responsible for O-demethylation of CD, CYP2D1 was also responsible for the O-deethylation of EM to M [3].
• Characterization of cytochrome P-450 2D1 activity in rat brain: high-affinity kinetics for dextromethorphan [4].

Biological context of Cyp2d9

• Substrates for cytochrome P450-2D1 exhibit a high affinity for sigma binding sites suggesting that sigma sites may be associated with the cytochrome P450-2D1 isozyme [5].
• The NH2-terminal amino acid sequences of P-450 UT-7 and UT-7b were the same as the amino acid sequences of CYP2D1 and CYP2D2 deduced from the cDNA, respectively, except for the lack of a terminal methionine for P-450 UT-7b [6].

Anatomical context of Cyp2d9

• Two P-450s with debrisoquine 4-hydroxylation activity, designated P-450 UT-7 and UT-7b, were purified and partially purified, respectively, from hepatic microsomes of untreated male rats [6].
• Antibody against P-450 UT-7, which also cross-reacted with P-450 UT-7b, inhibited lidocaine 3-hydroxylation in liver microsomes from untreated male rats, but had little effect on lidocaine N-deethylation [6].

Associations of Cyp2d9 with chemical compounds

• We investigated thermogenic and locomotor actions of MDMA in adult female Sprague-Dawley (CYP2D1 replete) and Dark Agouti rats [7].
• The Km and Vmax values for lidocaine 3-hydroxylation were 3.6 microM and 0.50 nmol/min/nmol of P-450 for P-450 UT-7, and 3.6 microM and 0.93 nmol/min/nmol of P-450 for P-450 UT-7b, respectively [6].
• These findings suggested that lidocaine 3-hydroxylation in hepatic microsomes from untreated male rats was catalyzed by P-450 UT-7 and/or UT-7b.P-450 UT-7 not containing 29 k-protein was obtained as the non-absorbed fraction from hydroxylapatite HPLC [6].

Enzymatic interactions of Cyp2d9

• In a reconstituted systems, P-450 UT-7 and UT-7b catalyzed lidocaine 3-hydroxylation and N-deethylation in the presence of the 29 k-protein [6].

Other interactions of Cyp2d9

• We believe that P450 UT-1, P450 UT-7 and P450 UT-8 are as yet unrecognized forms of cytochrome P-450 [8].

References