Reactome | CYP2D6 4-hydroxylates debrisoquine

CYP2D6 4-hydroxylates debrisoquine

Stable Identifier

R-HSA-211966

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane, endoplasmic reticulum lumen

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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
7903454	Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine Johansson, I, Lundqvist, E, Bertilsson, L, Dahl, ML, Sjöqvist, F, Ingelman-Sundberg, M	Proc Natl Acad Sci U S A	1993
6220203	Substrate specificity of the form of cytochrome P-450 catalyzing the 4-hydroxylation of debrisoquine in man Boobis, AR, Murray, S, Kahn, GC, Robertz, GM, Davies, DS	Mol Pharmacol	1983

Participants

Input

Output

Participant Of

hasEvent

Xenobiotics

Catalyst Activity

Title

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]

Physical Entity

Cytochrome P450 (CYP2D6 based) [endoplasmic reticulum membrane]

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 (0016712)

Orthologous Events

CYP2D6 4-hydroxylates debrisoquine (Bos taurus)

CYP2D6 4-hydroxylates debrisoquine (Danio rerio)

CYP2D6 4-hydroxylates debrisoquine (Dictyostelium discoideum)

CYP2D6 4-hydroxylates debrisoquine (Gallus gallus)

CYP2D6 4-hydroxylates debrisoquine (Mus musculus)

CYP2D6 4-hydroxylates debrisoquine (Rattus norvegicus)

CYP2D6 4-hydroxylates debrisoquine (Xenopus tropicalis)