![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
KJ Martell, KP Vatsis and WW Weber
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
The molecular genetic basis of N-acetylation polymorphism has been investigated in inbred mouse models of the human acetylation polymorphism. Two genomic clones, Nat1 and Nat2, were isolated from a C57BL/6J (B6) mouse (rapid acetylator) genomic library. The Nat1 and Nat2 genes both have intronless coding regions of 870 nucleotides and display greater than 47% deduced amino acid similarity with human, rabbit, and chicken N-acetyltransferases. Amplification of Nat1 and Nat2 from A/J (A) mouse (slow acetylator) genomic DNA by the polymerase chain reaction and subsequent sequencing revealed that Nat1 was identical in B6 and A mice, whereas Nat2 contained a single nucleotide change from adenine in B6 to thymine in A mice. This nucleotide substitution changes the deduced amino acid at position 99 from asparagine in B6 to isoleucine in A mice. Hydropathy analysis revealed that this amino acid change alters the hydropathy of the flanking peptide segment in NAT2 from hydrophilic in the B6 mouse to hydrophobic in the A mouse. The amino acid change occurs in a region of the gene where no polymorphism has yet been reported in human or rabbit NAT2 and may represent an important structural domain for N-acetyltransferase activity. Nat1 and Nat2 have the same 5' to 3' orientation in the B6 mouse; the two genes are separated by approximately 9 kilobases, with Nat1 located 5' of Nat2.
This article has been cited by other articles:
|
|
 |
|
  K. S. Sugamori, D. Brenneman, S. Wong, A. Gaedigk, V. Yu, H. Abramovici, R. Rozmahel, and D. M. Grant Effect of Arylamine Acetyltransferase Nat3 Gene Knockout on N-Acetylation in the Mouse Drug Metab. Dispos., July 1, 2007; 35(7): 1064 - 1070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Sugamori, S. Wong, A. Gaedigk, V. Yu, H. Abramovici, R. Rozmahel, and D. M. Grant Generation and Functional Characterization of Arylamine N-Acetyltransferase Nat1/Nat2Double-Knockout Mice Mol. Pharmacol., July 1, 2003; 64(1): 170 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Sim, M. Payton, M. Noble, and R. Minchin An update on genetic, structural and functional studies of arylamine N-acetyltransferases in eucaryotes and procaryotes Hum. Mol. Genet., October 1, 2000; 9(16): 2435 - 2441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Estrada, K. C. Kanelakis, G. N. Levy, and W. W. Weber Tissue- and Gender-Specific Expression of N-Acetyltransferase 2 (Nat2*) during Development of the Outbred Mouse Strain CD-1 Drug Metab. Dispos., February 1, 2000; 28(2): 139 - 146. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. W. Hein, M. A. Doll, A. J. Fretland, M. A. Leff, S. J. Webb, G. H. Xiao, U.-S. Devanaboyina, N. A. Nangju, and Y. Feng Molecular Genetics and Epidemiology of the NAT1 and NAT2 Acetylation Polymorphisms Cancer Epidemiol. Biomarkers Prev., January 1, 2000; 9(1): 29 - 42. [Abstract] [Full Text]
|
|
|
|
|
|
M. K. Mitchell, B. W. Futscher, and C. A. McQueen Developmental Expression of N-Acetyltransferases in C57BI/6 Mice Drug Metab. Dispos., February 1, 1999; 27(2): 261 - 264. [Abstract] [Full Text]
|
|
|
|
|
|
L. Estrada-Rodgers, G. N. Levy, and W. W. Weber Substrate Selectivity of Mouse N-Acetyltransferases 1, 2, and 3 Expressed in COS-1 Cells Drug Metab. Dispos., May 1, 1998; 26(5): 502 - 505. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
