CYP2D6
CYP2D6 (cytochrome P450 2D6, also known as CPD6, P450-DB1, CYP2D and P450C2D) is an endoplasmic reticulum monooxygenase of the cytochrome P450 family. It metabolises fatty acids, steroids, retinoids and a large share of commonly prescribed drugs. Browse Assay Genie's current range of CYP2D6 research reagents below, or read on for the biology behind the target.
CYP2D6 is a cytochrome P450 monooxygenase. Mechanistically, it uses molecular oxygen, inserting one oxygen atom into a substrate and reducing the second to water, with two electrons supplied by NADPH through cytochrome P450 reductase (NADPH--hemoprotein reductase). It catalyses the hydroxylation of carbon-hydrogen bonds and the epoxidation of double bonds in polyunsaturated fatty acids. It also converts the endocannabinoid anandamide to 20-HETE-EA and to epoxyeicosatrienoic acid ethanolamides, which may modulate endocannabinoid signalling. In sterol and vitamin A metabolism, it converts cholesterol towards 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. It also oxidises all-trans retinol to all-trans retinal, a precursor of all-trans-retinoic acid.
The enzyme is best known for drug metabolism. It is reported to metabolise as many as 25% of commonly prescribed drugs, including antidepressants, antipsychotics, analgesics, antitussives, beta adrenergic blocking agents, antiarrhythmics and antiemetics. The CYP2D6 gene encodes a protein that localises to the endoplasmic reticulum and belongs to the cytochrome P450 family 2 group. Alternatively spliced transcript variants encoding different isoforms have been described.
The CYP2D6 gene is highly polymorphic in the human population. Certain alleles give a poor metabolizer phenotype with reduced ability to metabolise substrates. Some poor metabolizers carry two null alleles, while in others the gene is absent. The gene can also vary in copy number, and ultrarapid metabolizers can carry three or more active copies. Earlier names reflect this history: the protein was described as a debrisoquine- and sparteine-metabolising cytochrome P450, subfamily IID, polypeptide 6.
CYP2D6 metabolises many antidepressants, antipsychotics, analgesics, beta blockers and antiarrhythmics, and its polymorphisms give poor to ultrarapid metabolizer phenotypes.
The enzyme epoxidises polyunsaturated fatty acids and converts anandamide to hydroxylated and epoxidated products that may modulate endocannabinoid signalling.
CYP2D6 oxidises all-trans retinol to all-trans retinal, a precursor of all-trans-retinoic acid.
CYP2D6 metabolises cholesterol towards 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis, and acts on steroid substrates.
CYP2D6 is a monooxygenase that inserts one oxygen atom into substrates using electrons from NADPH via cytochrome P450 reductase. It acts on fatty acids, steroids, retinoids and many drugs, including antidepressants, antipsychotics, beta blockers and antiarrhythmics.
Aliases include CPD6, P450-DB1, CYP2D, P450C2D and CYP2DL1. Older names refer to the debrisoquine- and sparteine-metabolising cytochrome P450, subfamily IID, polypeptide 6. Several symbols, such as CYP2D7P2 and CYP2D8P2, are previous pseudogene-related designations. Alternatively spliced transcripts encode different isoforms.
The gene is highly polymorphic. Some alleles are null, giving poor metabolizers, and in some individuals the gene is absent. Copy number can also vary, and three or more active copies are associated with the ultrarapid metabolizer phenotype.
Other cytochrome P450 family 2 members and related drug-, steroid- and retinoid-metabolising enzymes with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P10635; product specifications from Assay Genie datasheets.