Disease relevance of CYP2C18

• Cytochrome p450 2C (CYP2C) in ischemic heart injury and vascular dysfunction [1].

Psychiatry related information on CYP2C18

• Fifty adults with CP and chronic pain were interviewed to assess pain experience, the interference of pain on activities (BPI), depressive symptoms (CES-D), and coping strategies used for the pain (CSQ and CPCI) [2].

High impact information on CYP2C18

• The cytochrome P-450 2C18 gene was found by reverse transcription-PCR to represent the most abundantly expressed gene of the P-450 2C subfamily in human epidermis [3].
• Exon skipping and circular RNA formation in transcripts of the human cytochrome P-450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis [3].
• These data clearly implicate CYP3A in the formation of metabolite M4 and CYP2C in the synthesis of metabolite M5 [4].
• Correlation between CYP2C content or diazepam demethylation and the synthesis of metabolite M5 was highly positive [4].
• Reverse transcription-PCR analysis in human epidermis, using primers from CYP2C18 and CYP2C19, revealed products containing combinations between canonically defined exons of these two genes [5].

Biological context of CYP2C18

• Moreover, chimeric RNA species consisting of exons originating not only from the CYP2C8 and CYP2C18 genes, but also from the CYP2C19 gene were detected [6].
• There is a genetic polymorphism in humans in the metabolism of S-mephenytoin which has been suggested to be mediated by either CYP2C18 or CYP2C9 [7].
• Gene structure and upstream regulatory regions of human CYP2C9 and CYP2C18 [7].
• Another variant consisted of the nine typical CYP2C9 exons spliced after the CYP2C18 exon 1-like sequence through a segment of CYP2C9 5' flanking sequences [8].
• One splice variant was found to have an open reading frame starting at the canonical translation initiation codon of the CYP2C18 exon 1-like sequence [8].

Anatomical context of CYP2C18

• CYP2C18 mRNA was found only in the brain, uterus, mammary gland, kidney, and duodenum and CYP2C19 mRNA was found only in the duodenum [9].
• Since the CYP2C18 content of hepatic microsomes in humans is relatively low, CYP2C9, 2C19, and 3A4 might be the main isoforms of CYP that are responsible for tributyltin and triphenyltin metabolism in the human liver [10].
• A transgenic cell line was established by transfecting the recombinant plasmid of pREP9-CYP2C18 to Chinese hamster lung (CHL) cell [11].
• Using isolated rat hepatocytes in culture, we demonstrate that specific inhibition of either the CYP2C epoxygenase or the CYP4A omega-hydroxylase abrogates ciprofibrate-induced peroxisomal proliferation, whereas inhibition of other eicosanoid-synthesizing pathways had no effect [12].
• Midazolam and triazolam biotransformation in mouse and human liver microsomes: relative contribution of CYP3A and CYP2C isoforms [13].

Associations of CYP2C18 with chemical compounds

• CYP2C18 had the highest in vitro intrinsic clearance/catalytic efficiency (apparent Vmax/Km) in cyclophosphamide and ifosfamide activation, followed by 2C19 > 2C9 approximately 2C8 [14].
• CYP2A6, 2B6, 2C8, 2C9, 2C19, and 2D6 each showed a varying degree of low catalytic activity for estrogen 2-hydroxylation, whereas CYP2C18 and CYP2E1 did not show any detectable estrogen-hydroxylating activity [15].
• Although CYP2C18 is an efficient methoxychlor demethylase, its expression in liver is reportedly low or absent, suggesting a negligible role for this enzyme in methoxychlor metabolism [16].
• All of the tested CYPs, except CYP2A6 and CYP2C18, metabolized ethanol into significant amounts of acetaldehyde and displayed K(m) values around 10mM [17].
• In conclusion, our results show that enzymes of the CYP2C subfamily are mainly involved in verapamil O-demethylation [18].

Other interactions of CYP2C18

• Both D-703 and D-702 were formed by stably expressed CYP2C9 and CYP2C18, whereas incubation with CYP2C8 selectively yielded D-703 [18].
• After birth, hepatic CYP2D6 and CYP2C8/9 and CYP2C18/19 become active [19].
• Polymerase chain reaction-directed identification, cloning, and quantification of human CYP2C18 mRNA [20].
• It is concluded that the O-demethylation of naproxen (< or = 0.4 mM) is catalyzed by CYP2C subfamily members (CYP2C9/10) and CYP1A2 in human liver microsomes [21].
• Both CYP2D6 and CYP2C gene families are polymorphic; both families are important in antidepressant metabolism [22].

Analytical, diagnostic and therapeutic context of CYP2C18

• Rapid amplification of cDNA ends (RACE) and PCR amplifications of human liver cDNA revealed the presence of several intergenic species containing the CYP2C18 exon 1-like sequence spliced to different combinations of exonic and intronic sequences from the CYP2C9 gene [8].
• METHODS: The human CYP2C18 cDNA was amplified with reverse transcription-polymerase chain reaction (RT-PCR) from total RNAs extracted from human liver and cloned into pGEM-T vector [11].
• The enzyme activity of CYP2C18 to oxidate tolbutamide in postmitochondrial supernate (S9) fraction was determined by HPLC [23].
• Targeted antipeptide antibodies to cytochrome P450 2C18 based on epitope mapping of an inhibitory monoclonal antibody to P450 2C51 [24].
• Initial research has supported the reliability and validity of the CPCI [25].

References