Human cytochrome P450 4F3: structure, functions, and prospects.
Cytochrome P450 4F3 (CYP4F3), originally identified as one of the leukotriene B4 ω-hydroxylases, belongs to a CYP gene family that comprises several members, which participate in the metabolism of various endobiotics, as well as some xenobiotics. The CYP4F gene family is clustered in a 0.5-Mb stretch of genomic DNA on the p13 region of chromosome 19. Apart from the ω-hydroxylation of leukotriene B4 and prostaglandins, CYP4F3 is the main catalyst in the oxidation of fatty acid epoxides. CYP4F3 expression results from the synthesis of two distinct enzymes, CYP4F3A and CYP4F3B, which originate from the alternative splicing of a single pre-mRNA precursor molecule. Remarkably, the selection of either isoform is part of a tissue-specific control through which CYP3F3A is mostly expressed in leukocytes and CYP4F3B mostly in the liver. Recently, CYP4F3 single nucleotide polymorphisms have been incriminated in the onset of pathologies, including celiac or Crohn's diseases. Although much has been discovered in the regulation and function of CYP4F2, the closest CYP4F subfamily member, analyses of CYP4F3 enzymes lag somewhat behind in the field of our knowledge. In this short review, emphasis will be placed on the regulation and the functional roles of human CYP4F3.
INSERM U613-ECLA, Faculté de Médecine, Brest, France. laurent.corcos@inserm.fr
Laurent
L
Corcos
Danièle
D
Lucas
Catherine
C
Le Jossic-Corcos
Yvonne
Y
Dréano
Brigitte
B
Simon
Emmanuelle
E
Plée-Gautier
Yolande
Y
Amet
Jean-Pierre
JP
Salaün
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072470:Cytochrome P450 Family 4; D005227:Fatty Acids / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015262:Xenobiotics / Q000378:metabolism
D005227:Fatty Acids; D012333:RNA, Messenger; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; C465349:CYP4F3 protein, human