QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lattard, V. Articles by Cashman, J. R. Search for Related Content PubMed PubMed Citation Articles by Lattard, V. Articles by Cashman, J. R.

Alternative Processing Events in Human FMO Genes

Human BioMolecular Research Institute, San Diego, California

In humans, flavin-containing monooxygenase (FMO) functional diversity is determined by the expression of five FMO genes, named FMO1 to FMO5, and their variants. In this study, we systematically analyzed transcripts of FMO1 to FMO5 in different human tissues by reverse-transcription-polymerase chain reaction and identified a large number of splice variants. Exon skipping was the major splicing event observed. Normally spliced transcripts were generally the prominent transcript detected. For FMO1, FMO2, and FMO3, two to three different splice variants were identified, and their corresponding expression was always low in the tissues examined. For FMO5 and particularly for FMO4, more complex alternative splice patterns were observed, with five and seven splice variants detected, respectively. Most identified FMO splice variants either caused a frame-shift or lacked essential functional sites. The corresponding transcripts were therefore incapable of encoding a functional enzyme and were not analyzed further in this study. However, a common in-frame exon 3- (exon 4 for FMO4) deleted variant, leading to the deletion of 63 amino acids, was identified for FMO1, FMO3, FMO4, and FMO5. To examine the functional importance of exon 3-deletion, FMO1, FMO3, FMO4 and the corresponding exon-deleted proteins were expressed as fusion proteins. Activity studies were done with two selective functional FMO substrates, methimazole, and 10-(N,N-dimethylaminopentyl)-2-(trifluoromethyl)phenothiazine and exon 3- (exon 4 for FMO4) deleted FMOs were not able to catalyze the S- and N-oxygenation of these substrates, respectively. It is not clear whether these FMO splice variants can oxygenate other substrates, including those that remain to be discovered.

Address correspondence to: John R. Cashman; Human BioMolecular Research Institute, 5310 Eastgate Mall, San Diego CA, 92121. E-mail: jcashman{at}hbri.org

This article has been cited by other articles:

				G. Rodriguez-Fuentes, R. Aparicio-Fabre, Q. Li, and D. Schlenk Osmotic Regulation of a Novel Flavin-Containing Monooxygenase in Primary Cultured Cells from Rainbow Trout (Oncorhynchus mykiss) Drug Metab. Dispos., July 1, 2008; 36(7): 1212 - 1217. [Abstract] [Full Text] [PDF]

				A. Alfieri, E. Malito, R. Orru, M. W. Fraaije, and A. Mattevi Revealing the moonlighting role of NADP in the structure of a flavin-containing monooxygenase PNAS, May 6, 2008; 105(18): 6572 - 6577. [Abstract] [Full Text] [PDF]

				T. Borbas, J. Zhang, M. A. Cerny, I. Liko, and J. R. Cashman Investigation of Structure and Function of a Catalytically Efficient Variant of the Human Flavin-Containing Monooxygenase Form 3 Drug Metab. Dispos., December 1, 2006; 34(12): 1995 - 2002. [Abstract] [Full Text] [PDF]

				J. Zhang and J. R. Cashman QUANTITATIVE ANALYSIS OF FMO GENE mRNA LEVELS IN HUMAN TISSUES Drug Metab. Dispos., January 1, 2006; 34(1): 19 - 26. [Abstract] [Full Text] [PDF]

				S. B. Koukouritaki, M. T. Poch, E. T. Cabacungan, D. G. McCarver, and R. N. Hines Discovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants Mol. Pharmacol., August 1, 2005; 68(2): 383 - 392. [Abstract] [Full Text] [PDF]