CYP2D6 4-hydroxylates debrisoquine

Stable Identifier
Reaction [transition]
Homo sapiens
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CYP2D6 (debrisoquine 4-hydroxylase) has a wide substrate specificity and is an important cytochrme P450 in drug metabolism. It has extensive genetic polymorphism (called the debrisoquine/sparteine oxidation polymorphism) that influences its expression and function.The polymorphism is responsible for populations being poor metabolizers (PM) or extensive metabolizers (EM, normal). Approximately 10% of Caucasians and less than 1% of Asians lack the CYP2D6 protein because of two null alleles which do not encode the functional product. Further polymorphisms discovered recently have identified ultrarapid metabolizers (PM) (alleles with multiple gene copies) and intermediate metabolizers (IM) (deficiency in their metabolism capacity) (Zanger UM et al, 2004).

Literature References
PubMed ID Title Journal Year
6220203 Substrate specificity of the form of cytochrome P-450 catalyzing the 4-hydroxylation of debrisoquine in man

Kahn, GC, Davies, DS, Murray, S, Robertz, GM, Boobis, AR

Mol Pharmacol 1983
7903454 Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine

Sjöqvist, F, Lundqvist, E, Bertilsson, L, Johansson, I, Ingelman-Sundberg, M, Dahl, ML

Proc Natl Acad Sci U S A 1993
Catalyst Activity

oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen of Cytochrome P450 (CYP2D6 based) [endoplasmic reticulum membrane]

Orthologous Events
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