|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 273, Issue 46, 30599-30607, November 13, 1998
From the Flavin-containing monooxygenases
(FMOs) are NADPH-dependent flavoenzymes that catalyze
the oxidation of heteroatom centers in numerous drugs and xenobiotics.
FMO2, or "pulmonary" FMO, one of five forms of the enzyme
identified in mammals, is expressed predominantly in lung and differs
from other FMOs in that it can catalyze the N-oxidation of
certain primary alkylamines. We describe here the isolation and
characterization of cDNAs for human FMO2. Analysis of the sequence
of the cDNAs and of a section of the corresponding gene revealed
that the major FMO2 allele of humans encodes a polypeptide
that, compared with the orthologous protein of other mammals, lacks 64 amino acid residues from its C terminus. Heterologous expression of the
cDNA revealed that the truncated polypeptide was catalytically
inactive. The nonsense mutation that gave rise to the truncated
polypeptide, a C
The Flavin-containing Monooxygenase 2 Gene (FMO2)
of Humans, but Not of Other Primates, Encodes a Truncated,
Nonfunctional Protein
,,,
Laboratory of Molecular Biology, Department
of Biochemistry, Queen Mary and Westfield College, University of
London, London E1 4NS, United Kingdom, the ¶ Department of
Biochemistry and Molecular Biology, University College London,
London WC1E 6BT, United Kingdom, and ** Molecular Toxicology, Imperial
College School of Medicine, London W2 1PG, United Kingdom
T transition in codon 472, is not present in the
FMO2 gene of closely related primates, including gorilla
and chimpanzee, and must therefore have arisen in the human lineage
after the divergence of the Homo and Pan clades. Possible mechanisms
for the fixation of the mutation in the human population and the
potential significance of the loss of functional FMO2 in humans are discussed.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. K. Krueger, M. C. Henderson, L. K. Siddens, J. E. VanDyke, A. D. Benninghoff, P. A. Karplus, B. Furnes, D. Schlenk, and D. E. Williams Characterization of Sulfoxygenation and Structural Implications of Human Flavin-Containing Monooxygenase Isoform 2 (FMO2.1) Variants S195L and N413K Drug Metab. Dispos., August 1, 2009; 37(8): 1785 - 1791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Francois, C. R. Nishida, P. R. O. de Montellano, I. R. Phillips, and E. A. Shephard Human Flavin-Containing Monooxygenase 2.1 Catalyzes Oxygenation of the Antitubercular Drugs Thiacetazone and Ethionamide Drug Metab. Dispos., January 1, 2009; 37(1): 178 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Krueger, L. K. Siddens, S. R. Martin, Z. Yu, C. B. Pereira, E. T. Cabacungan, R. N. Hines, K. G. Ardlie, J. L. Raucy, and D. E. Williams DIFFERENCES IN FMO2*1 ALLELIC FREQUENCY BETWEEN HISPANICS OF PUERTO RICAN AND MEXICAN DESCENT Drug Metab. Dispos., December 1, 2004; 32(12): 1337 - 1340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Calestani, J. P. Rast, and E. H. Davidson Isolation of pigment cell specific genes in the sea urchin embryo by differential macroarray screening Development, October 1, 2003; 130(19): 4587 - 4596. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Furnes, J. Feng, S. S. Sommer, and D. Schlenk Identification of Novel Variants of the Flavin-Containing Monooxygenase Gene Family in African Americans Drug Metab. Dispos., February 1, 2003; 31(2): 187 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Krause, L. H. Lash, and A. A. Elfarra Human Kidney Flavin-Containing Monooxygenases and Their Potential Roles in Cysteine S-Conjugate Metabolism and Nephrotoxicity J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 185 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Cashman and J. Zhang Interindividual Differences of Human Flavin-Containing Monooxygenase 3: Genetic Polymorphisms and Functional Variation Drug Metab. Dispos., October 1, 2002; 30(10): 1043 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Krueger, S. R. Martin, M.-F. Yueh, C. B. Pereira, and D. E. Williams Identification of Active Flavin-Containing Monooxygenase Isoform 2 in Human Lung and Characterization of Expressed Protein Drug Metab. Dispos., January 1, 2002; 30(1): 34 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. N. Hines, Z. Luo, T. Cresteil, X. Ding, R. A. Prough, J. L. Fitzpatrick, S. L. Ripp, K. C. Falkner, N.-L. Ge, A. Levine, et al. Molecular Regulation of Genes Encoding Xenobiotic-Metabolizing Enzymes: Mechanisms Involving Endogenous Factors Drug Metab. Dispos., April 13, 2001; 29(5): 623 - 633. [Abstract] [Full Text]
|
|
|
|
|
|
S. K. Krueger, M.-F. Yueh, S. R. Martin, C. B. Pereira, and D. E. Williams Characterization of Expressed Full-Length and Truncated FMO2 from Rhesus Monkey Drug Metab. Dispos., April 13, 2001; 29(5): 693 - 700. [Abstract] [Full Text]
|
|
|
|
|
|
M. G. Pike, D. C. Mays, D. W. Macomber, and J. J. Lipsky Metabolism of a Disulfiram Metabolite, S-Methyl N,N-Diethyldithiocarbamate, by Flavin Monooxygenase in Human Renal Microsomes Drug Metab. Dispos., February 1, 2001; 29(2): 127 - 132. [Abstract] [Full Text]
|
|
|
|
|
|
Y. M. Kim and D. M. Ziegler Size Limits of Thiocarbamides Accepted as Substrates by Human Flavin-Containing Monooxygenase 1 Drug Metab. Dispos., August 1, 2000; 28(8): 1003 - 1006. [Abstract] [Full Text]
|
|
|
|
|
|
B. J. Ring, S. A. Wrighton, S. L. K. Aldridge, K. Hansen, B. Haehner, and L. A. Shipley Flavin-Containing Monooxygenase-Mediated N-Oxidation of the M1-Muscarinic Agonist Xanomeline Drug Metab. Dispos., October 1, 1999; 27(10): 1099 - 1103. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |