Disease relevance of CYP4F12

• These data on CYP4F12 genetic polymorphism provide tools for further studies of association with pathological processes involving an inflammatory component and with variations in anti-histaminic drug response [1].

High impact information on CYP4F12

• Human CYP4F12 genetic polymorphism: identification and functional characterization of seven variant allozymes [1].
• Considering the nature and location of the polymorphisms characterizing the CYP4F12*v1 and *v2, the functional relevance of those two allelic variants was further examined by transfecting different cell lines with constructs of the related region of the CYP4F12/luciferase reporter gene [2].
• In the present study, we report the further identification of single nucleotide polymorphisms in the coding sequence of the CYP4F12 gene [1].
• Both alleles lead to a significant decrease of CYP4F12 gene expression in HepG2 cell line and, therefore, are likely to determine interindividual differences in CYP4F12 gene expression [2].
• The catalytic activity of recombinant CYP2J2 was much higher than that of CYP4F12 [3].

Biological context of CYP4F12

• These results indicate that CYP4F12 has a different profile of substrate specificity from other CYP4F isoforms, enzymes responsible for metabolizing endogenous autacoids, therefore suggesting that it may play an important role in xenobiotic biotransformation in the human small intestine [4].
• The CYP4F12 gene contained 13 exons and was located at chromosome 19p13 [5].
• A cDNA encoding a novel human CYP4F enzyme (designated CYP4F12) was cloned by PCR from a human small intestine cDNA library [4].
• Interestingly, CYP4F12 catalyzes the hydroxylation of the antihistamine ebastine with significantly higher catalytic activity relative to CYP4F2 (385 vs 5 pmol/min/nmol P450) [4].
• Prominent CYP4F12 immunoreactivity occurred, inter alia, in the epithelial cells of the gastrointestinal tract (stomach, small intestine, and colon), collecting tubules, transitional epithelium, ovarian follicles, the endothelium of microvessels of placental villi (first trimester), and epidermis [6].

Anatomical context of CYP4F12

• Involvement of CYP2J2 and CYP4F12 in the metabolism of ebastine in human intestinal microsomes [3].
• RT-PCR analysis demonstrated that CYP4F12 is expressed in human small intestine and liver [4].
• Enzymatic activity assay, immunocytochemical staining, and reverse transcription-polymerase chain reaction (RT-PCR) analysis of human leukocytes showed that polymorphonuclear leukocytes (PMNs) expressed CYP4F3B and CYP4F12 in addition to CYP4F3 [7].
• The HL60 cells, which were differentiated into PMN-like shapes by treatment with all-trans-retinoic acid (RA), also expressed CYP4F3, CYP4F3B and CYP4F12 [7].
• CYP4F12 mRNA could be detected in seminal vesicles and prostate gland by reverse transcription-PCR [6].

Associations of CYP4F12 with chemical compounds

• 1. CYP4F12, expressed in yeast, oxidized arachidonic acid to 18-hydroxyarachidonic acid, and the omega-side chain of two stable prostaglandin (PG) H(2) analogs (11,9-epoxymethano-PGH(2) and 9,11-diazo-15-deoxy-PGH(2)) [5].
• CYP4F enzymes with omega-hydroxylase activity contain a heme-binding Glu residue, whereas CYP4F8 (and CYP4F12) with omega2- and omega 3-hydroxylase activities has a Gly residue in this position of SRS-4 [8].

Other interactions of CYP4F12

• Recombinant CYP4F8 and CYP4F12 metabolize prostaglandin H2 (PGH2) analogs by omega2- and omega3-hydroxylation and arachidonic acid (20:4n-6) by omega3-hydroxylation [8].

Analytical, diagnostic and therapeutic context of CYP4F12

• Northern blot analysis suggested three major transcripts of CYP4F12, which were detected in liver, kidney, colon, small intestine and heart [5].
• An antipeptide polyclonal antibody was raised against the C-terminal of CYP4F12 (PLNVGLQ), evaluated by Western blot analysis and used for immunohistological analysis of 50 human tissues [6].

References