Cytochrome P450 2C19

Function

A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position. Catalyzes the epoxidation of double bonds of PUFA. Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol. Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position.

Classification

Family (Pfam)

PF00067 p450

InterPro

Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-I, Cyt_P450_sf, Cytochrome_P450_fam2

Functional cluster

Cytochrome P450 & Heme Enzymes

Experimental structures · PDB · 1

• 4GQS X-ray 2.87A

A predicted model is available from AlphaFold.

Gene Ontology · 22

• GO:0005737 cytoplasm
• GO:0005789 endoplasmic reticulum membrane
• GO:0043231 intracellular membrane-bounded organelle
• GO:0052741 (R)-limonene 6-monooxygenase activity
• GO:0018675 (S)-limonene 6-monooxygenase activity
• GO:0018676 (S)-limonene 7-monooxygenase activity
• GO:0019899 enzyme binding
• GO:0020037 heme binding
• GO:0005506 iron ion binding
• GO:0120319 long-chain fatty acid omega-1 hydroxylase activity
• GO:0004497 monooxygenase activity
• GO:0016491 oxidoreductase activity
• GO:0016712 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
• GO:0019825 oxygen binding
• GO:0008395 steroid hydroxylase activity
• GO:0019373 epoxygenase P450 pathway
• GO:0001676 long-chain fatty acid metabolic process
• GO:0016098 monoterpenoid metabolic process
• GO:0097267 omega-hydroxylase P450 pathway
• GO:0008202 steroid metabolic process
• GO:0042178 xenobiotic catabolic process
• GO:0006805 xenobiotic metabolic process

Disease associations

• obsolete drug metabolism, poor, Cyp2C19-related MONDO:0012294

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Cytochrome P450 2C9 0.99
• Cytochrome P450 2C6 0.99
• Cytochrome P450 2C18 0.99
• Cytochrome P450 2C29 0.99
• Cytochrome P450 2C4 0.99
• Cytochrome P450 2C14 0.98
• Cytochrome P450 2C16 0.98
• Cytochrome P450 2C1 0.98
• Cytochrome P450 2C39 0.98
• Cytochrome P450 2C5 0.98
• Cytochrome P450 2C38 0.98
• Cytochrome P450 2C11 0.98

Co-cited proteins · studied together in the literature

• Cytochrome P450 2C18 2 shared papers
• Cytochrome P450 2J2 2 shared papers
• Cytochrome P450 2C9 3 shared papers
• Cytochrome P450 2C8 3 shared papers
• Cytochrome P450 1A1 4 shared papers
• Cytochrome P450 2D6 3 shared papers
• Cytochrome P450 2E1 2 shared papers
• Cytochrome P450 1B1 1 shared papers
• Cytochrome P450 4F3 1 shared papers
• Cytochrome P450 4F2 1 shared papers
• Cytochrome P450 1A1 1 shared papers
• Cytochrome P450 1A2 2 shared papers

Literature · 22 cited papers

• Worldwide Distribution of Cytochrome P450 Alleles: A Meta-analysis of Population-scale Sequencing Projects. Clin. Pharmacol. Ther. · 2017
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems. Antimicrob. Agents Chemother. · 2013
• Structural characterization of human cytochrome P450 2C19: active site differences between P450s 2C8, 2C9, and 2C19. J. Biol. Chem. · 2012
• Analysis of epoxyeicosatrienoic acids by chiral liquid chromatography/electron capture atmospheric pressure chemical ionization mass spectrometry using [13C]-analog internal standards. Rapid Commun. Mass Spectrom. · 2010
• Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450. J. Lipid Res. · 2010
• Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism. J. Lipid Res. · 2008
• Genetic variations and haplotypes of CYP2C19 in a Japanese population. Drug Metab. Pharmacokinet. · 2005
• A novel single nucleotide polymorphism (SNP) of the CYP2C19 gene in a Japanese subject with lowered capacity of mephobarbital 4'-hydroxylation. Drug Metab. Pharmacokinet. · 2004
• Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics · 2004
• The DNA sequence and comparative analysis of human chromosome 10. Nature · 2004
• Identification and functional characterization of new potentially defective alleles of human CYP2C19. Pharmacogenetics · 2002
• … and 10 more in the literature graph