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- Table of Contents
Facts about Cytochrome P450 2D6.
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Human | |
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Gene Name: | CYP2D6 |
Uniprot: | P10635 |
Entrez: | 1565 |
Belongs to: |
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cytochrome P450 family |
CPD6P450DB1; CYP2D; CYP2D7AP; CYP2D7BP; CYP2D7P2; CYP2D8P2; CYP2DL1; CYPIID6; cytochrome P450 2D6; cytochrome P450, family 2, subfamily D, polypeptide 6; cytochrome P450, family 2, subfamily D, polypeptide 7 pseudogene 2; cytochrome P450, family 2, subfamily D, polypeptide 8 pseudogene 2; cytochrome P450, subfamily II (debrisoquine, sparteine, etc., -metabolising); cytochrome P450, subfamily IID (debrisoquine, sparteine, etc.; cytochrome P450, subfamily IID (debrisoquine, sparteine, etc., -metabolising); cytochrome P450, subfamily IID (debrisoquine, sparteine, etc., -metabolizing); Cytochrome
Mass (kDA):
55.769 kDA
Human | |
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Location: | 22q13.2 |
Sequence: | 22; NC_000022.11 (42126499..42130810, complement) |
Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
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CYP2D6 is an enzyme in the metabolic process that is involved in the metabolism of various drugs. This enzyme can metabolize drugs with amine functional group such as beta-blockers and anticholinergics, carvedilol and metoprolol, as well as risperidone. CYP2D6 also metabolizes many other drugs, including beta blockers and antiarrhythmics. Of the more popular drugs metabolized by CYP2D6, tamoxifen and celecoxib are known substrates of CYP2D6.
CYP2D6 is responsible for the metabolism of around a quarter all of the most commonly prescribed drugs. These include beta-blockers and antidepressants as well as opioids, narcotics, and antiemetics. The majority of patients have CYP2D6*4 (the most frequently occurring loss-of-function allele in Caucasian individuals). Functionally relevant copy number variations (CNVs) are also found in CYP2D6. These CNVs could increase the metabolism of CYP2D6 substrates.
CYP2D6, despite its significance in human metabolism, is complex enzyme with complicated pharmacology. Its polymorphisms cause decreased or no enzyme activity. In turn, medications that are metabolized by CYP2D6 are more likely to undergo unexpected changes in their pharmacokinetic profile. The presence of a functional enzyme might be required to minimize adverse reactions or improve safety.
Pharmacogenetic variability can also affect CNS sensitivity for ADRs. This enzyme may play a significant role in the homeostasis of brain biochemistry by being a part of a permanent role. Polymorphisms in CYP2D6 gene have been associated with vigilance, alertness and continued attention. These associations have also been linked with functional magnetic resonance imaging.
The frequency of functional CYP2D6 duplications is the highest for Greece and the lowest for the Scandinavian population. From northern to southern European populations, the frequency of ultrarapid metabolizers decreases. Additionally in the Middle East and North-East Africa, CYP2D6 duplication is most common within the populace. The metabolic activity of different ethnic groups of CYP2D6 can be quite significant.
These differences in drug efficacy must not be ignored. Before prescribing any medication, it is essential to look at the CYP2D6-related dizziness. Furthermore, the variation in hepatic-cytochrome 2D6 levels could alter the efficacy of several commonly prescribed medications. Hydrocodone is processed by CYP2D6. Hydromorphone, a fivefold stronger opioid than hydrocodone, is much more potent when consumed by those with an overactive CYP2D6 gene.
The most commonly used CYP2D6*17 reduced allele in the CYP2D6 variants is the most widespread. In Arab populations where the mutated variant is prevalent, its prevalence was the highest in Egypt, Saudi Arabia, and Algeria, while the lowest frequency was found in Somalia and Yemen. Moreover, CYP2D6*17 is more prevalent in Africans than Caucasians.
The CYP2D6 genetic locus is on chromosome 22, and it has three major mutated variants that are CYP2D6*4 and CYP2D6*17. The CYP2D6*10 allele is defined by the alteration 100C, however, it is also present in 22 other alleles, including the functional CYP2D6*4 allele. It is possible to underestimate the frequency of an allele by assigning it to only one of these alleles.
The CYP2D6*17 mutant variant is the first polymorphic allel to be found in the human cytochrome P450 genes. Numerous mutations are found in this gene, and each mutation affects the enzyme's catalytic characteristics. The altered enzyme's affinity to CYP2D6 substrates results in a decrease in activity. Additionally, CYP2D6*17 can be found in boster cells.
UNPHASEDv was used to analyze the CYP2D6 haplotypes. 3.1.765. The analyses adjusted the age at sampling as well as the additive model. The significance level for haplotype-based analyses was 0.05 and haplotypes with a frequency of 1% or more were ruled out.
Three functional mutations exist in the CYP2D6*17 variant. It has been isolated from individuals in Zimbabwe who suffer from impaired drug metabolism. In order to investigate whether these mutations affect the enzyme's function, the CYP2D6 cDNAs bearing different combinations of the three mutations were examined in COS-1 cells. The enzyme's activity was not affected by the T107I substitution.
In addition to finding CYP2D6 alleles, a thorough study on their genetic makeup is needed to improve the outcome of clinical trials. This study will uncover many therapeutic possibilities. Future studies will help to identify the safety and effectiveness of CYP2D6 metabolized drugs.
The CYP2D6*17 gene, which is the most polymorphic CYP2D6 gene is the one most extensively studied. The gene is highly polymorphic and has more than 100 variant alleles. The polymorphic alleles confer an ultrarapid metabolism characteristic. The polymorphism is also classified based on the number of gene copies. CYP2D6*1X2 is an illustration of two copies the gene. CYP2D6*17XN, on the other hand, denotes a mutated copy with no metabolic phenotype.
The cytochrome P450 2D6 isoenzyme is responsible for the metabolic processing of approximately 25 percent of the most commonly used drugs. The impact of CYP2D6's metabolism on drug efficacy and safety was recently studied by 365 in-patients with psychiatric illnesses. Patients with below or above-median CYP2D6 status had longer hospital stays and delayed onset of response in comparison to those with extensive metabolizers. Intermediate metabolizers were also more likely to suffer adverse effects than those above and below-median CYP2D6-dependent metabolism.
Genetic variation affects CYP2D6 dependent metabolism. There are three types of CYP2D6 polymorphisms: increased, decreased, or nonfunctional enzyme activity. Individuals who lack functional enzyme activity are called poor metabolizers, whereas those with a single functional allele are referred to as excessive metabolizers. People who have multiple gene copies or drugs that inhibit the activity both of the exon and cytochrome P450 enzymes are rapid metabolizers.
In addition to the polymorphic CYP2D6 gene The CYP2D6 genotype is a significant factor for the efficacy of drugs. Genetic testing shows polymorphisms in CYP2D6 that influence drug pharmacogenicity. This research can help doctors tailor drug therapies. The results could also aid in the prevention of porphyria.
A study on black Zimbabweans found that CYP2D6 polymorphism was discovered to be more prevalent in nonporphyric persons as compared to Asians. People with the CYP2D6 polymorphism had higher levels of hepatic alteration and higher iron levels. Unmetabolized chemicals could remain in their bodies and cause harm. PM has been linked to breast cancer as well as leukemia.
CYP2D6 is the second-most popular drug metabolizer, is also a common one. Approximately 7% of Caucasians, and one percent of Orientals, have CYP2D6 deficiencies. The enzyme is highly multimorphic. People with polymorphic CYP2D6 show varying degrees of activity. Some patients suffering from CYP2D6 deficiencies show little or no activity. Others with CYP2D6 deficiency are large metabolizers who have low activity are intermediate metabolizers.
Scientists can make use of an anti-CYP2D6 antibody to determine the role of an enzyme. This antibody reacts with Human CYP2D6. It has an expected shelf-life of 1 year. The CYP2D6 marker is a metabolite in many different kinds of drugs. Boster Bio anti-CYP2D6 antibodies can be stored at -20°C for up to one year. The Boster Bio anti-CYP2D6 antibody is evaluated against known positive and negative samples by immunofluorescence.
PMID: 3410476 by Gonzalez F.J., et al. Human debrisoquine 4-hydroxylase (P450IID1): cDNA and deduced amino acid sequence and assignment of the CYP2D locus to chromosome 22.
PMID: 3123997 by Gonzalez F.J., et al. Characterization of the common genetic defect in humans deficient in debrisoquine metabolism.