Cytochrome P-450 CYP3A

A cytochrome P-450 monooxygenase that is involved in an NADPH-dependent electron transport pathway by oxidizing a variety of structurally unrelated compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.

Also Known As:

Networked: 287 relevant articles (14 outcomes, 62 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	van Schaik, Ron H N: 6 articles (09/2015 - 12/2004)
2.	Mathijssen, Ron H J: 5 articles (09/2015 - 10/2005)
3.	Liddle, Christopher: 5 articles (09/2013 - 03/2004)
4.	Clarke, Stephen J: 5 articles (09/2013 - 12/2004)
5.	Beijnen, Jos H: 4 articles (10/2015 - 05/2007)
6.	Verweij, Jaap: 4 articles (09/2015 - 12/2004)
7.	Dilger, Karin: 4 articles (01/2013 - 03/2005)
8.	Kaneshiro, Yasunori: 4 articles (11/2009 - 10/2006)
9.	Takaoka, Kunio: 4 articles (11/2009 - 10/2006)
10.	Hoffer, Christine: 4 articles (10/2005 - 03/2003)

Related Diseases

1.	Neoplasms (Cancer) 07/01/2003 - "We evaluated whether SNPs in the cytochrome P450 3A family (CYP3A4*1B, CYP3A5*3 and CYP3A5*6) were associated with relapse risk on a national Children's Cancer Group (CCG) paediatric ALL trial (CCG-1891). " 11/01/2007 - "Multiplex polymerase chain reaction (PCR) analysis and fluorescence in situ hybridization (FISH) analysis showed genomic gains affecting CYP3A and MDR1 genes in T-cell lines and primary tumors, suggesting that this could be the mechanism underlying the tumoral expression variation. " 01/01/2007 - "Further correlation was obtained between development of multidrug resistance in cancer cells and a concomitant decrease in inducibility of CYP1A and CYP3A drug metabolizing genes. " 06/01/2006 - "Tumors with increased CYP3A copy number (via amplification or increased chromosome 7q) would be expected to show reduced cytotoxicity to some chemotherapeutic drugs and potentially an increase in the outgrowth of drug resistant tumors." 10/15/2005 - "The studied genetic variants in CYP3A4 and CYP3A5 are unlikely to have an important functional significance to phenotypic CYP3A activity in patients with cancer."
2.	Breast Neoplasms (Breast Cancer) 01/01/2014 - "Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study." 05/02/2012 - "Genetic variation in noncoding sequences flanking the CYP3A locus contributes to variance in premenopausal E1G levels and is associated with the risk of breast cancer in younger patients. " 01/01/2005 - "In conclusion, the expression of CYP3A in breast cancer may be less frequent in Japanese population although the expression of CYP3A has been reported in 20% of breast cancer in Caucasian, suggesting that the CYP3A expression in breast cancer may be dependent on ethnic groups. " 09/01/2003 - "Hence, it will be significant to perform more work to determine the association between CYP3A activity and breast cancer susceptibility. " 09/01/2003 - "Relationship between CYP3A activity and breast cancer susceptibility in Chinese Han women."
3.	Prostatic Neoplasms (Prostate Cancer) 12/01/2010 - "In line with this, no significant associations were observed for CYP3A genotypes and prostate cancer incidence." 04/01/2006 - "However, as exemplified by the controversial association between CYP3A4*1B and prostate cancer, the detection of clinical effects of CYP3A gene variants will be difficult. " 12/01/2010 - "Cytochrome P450 3A gene variation, steroid hormone serum levels and prostate cancer--The Rotterdam Study." 12/01/2010 - "To study if polymorphisms in genes encoding for CYP3A enzymes, that play a role in steroid hormone metabolism, affect steroid hormone serum levels and prostate cancer incidence or mortality. " 02/01/2014 - "Mass spectrometry revealed that overexpression of CYP3A protein in prostate cancer cells resulted in a significant increase in the oxidative inactivation of testosterone and DHEA to their 6-β-hydroxy-testosterone and 16-α-hydroxy-DHEA metabolites, respectively. "
4.	Asthma (Bronchial Asthma) 03/01/2007 - "The aim of this study was to investigate the effects of roflumilast, an investigational PDE4 inhibitor for the treatment of COPD and asthma, on the pharmacokinetics of the CYP3A probe drug midazolam and its major metabolites. " 01/01/2013 - "Inhaled glucocorticoids are the first-line treatment for patients with persistent asthma.  However, approximately thirty percent of patients exhibit glucocorticoid insensitivity, which may involve excess metabolic clearance of the glucocorticoids by CYP3A enzymes in the lung.  CYP3A4, 3A5, and 3A7 enzymes metabolize glucocorticoids, which in turn induce CYP3A genes.  However, the mechanism of CYP3A5 mRNA regulation by glucocorticoids in lung cells has not been determined.  In hepatocytes, glucocorticoids bind to the glucocorticoid receptor (GR), which induces the expression of the constitutive androstane receptor or pregnane X receptor; both of which bind to the retinoid X receptor alpha, leading to the induction of CYP3A4, 3A5, and 3A7.  There is also evidence to suggest a direct induction of CYP3A5 by GR activation in liver cells. " 01/01/2013 - "Inhaled glucocorticoids are the first-line treatment for patients with persistent asthma.  However, approximately thirty percent of patients exhibit glucocorticoid insensitivity, which may involve excess metabolic clearance of the glucocorticoids by CYP3A enzymes in the lung.  CYP3A4, 3A5, and 3A7 enzymes metabolize glucocorticoids, which in turn induce CYP3A genes.  However, the mechanism of CYP3A5 mRNA regulation by glucocorticoids in lung cells has not been determined.  In hepatocytes, glucocorticoids bind to the glucocorticoid receptor (GR), which induces the expression of the constitutive androstane receptor or pregnane X receptor; both of which bind to the retinoid X receptor alpha, leading to the induction of CYP3A4, 3A5, and 3A7.  There is also evidence to suggest a direct induction of CYP3A5 by GR activation in liver cells. "
5.	Fibrosis (Cirrhosis) 11/01/2013 - "SB showed powerful hepatoprotective effects, and anti-inflammatory and anti-fibrosis effects, and reversed the loss of CYP3A and PXR in TAA-injured rat liver, and decreased PXR translocation into the cell nucleus. " 04/01/2009 - "Therefore, patients with advanced cirrhosis may have greater drug exposure following oral dosing as a result of both impaired liver function and decreased intestinal CYP3A expression and activity." 04/01/2009 - "Greater decreases in CYP3A expression were seen in subjects with more severe cirrhosis. " 04/01/2009 - "Reduced duodenal cytochrome P450 3A protein expression and catalytic activity in patients with cirrhosis." 12/01/2001 - "As expected, hepatic CYP3A activity was reduced in cirrhosis. "

Related Drugs and Biologics

1.	Enzymes
2.	Midazolam (Versed)
3.	Cytochrome P-450 Enzyme System (Cytochrome P450)
4.	pregnane X receptor
5.	Messenger RNA (mRNA)
6.	docetaxel (Taxotere)
7.	Glucocorticoids
8.	constitutive androstane receptor
9.	Tamoxifen
10.	Retinoid X Receptor alpha

Related Therapies and Procedures

1.	Kidney Transplantation
2.	Therapeutics
3.	Heterologous Transplantation (Xenotransplantation)
4.	Drug Therapy (Chemotherapy)
5.	Ligation