Identification of a novel allele at the human NAT1 acetyltransferase locus

Biochemical and Biophysical Research Communications
M A DollD W Hein

Abstract

Humans possess two N-acetyltransferase isozymes (NAT1 and NAT2). We cloned and sequenced a novel NAT1 allele (Genbank HSU 80835) that contained nucleotide substitutions at -344 (C-->T), -40 (A-->T), 445 [G-->A(Val-->Ile)], 459 [G-->A(silent)], 640 [T-->G(Ser-->Ala)], a 9 base pair deletion between nucleotides 1065 and 1090, and 1095 (C-->A). The novel NAT1 allele which we have designated NAT1*17 is similar to NAT1*11 except for a G445A substitution (Val149-->Ile) in the NAT1 coding region. The G445A (Val149-->Ile) substitution yielded no significant changes in levels of immunoreactivity, as detected by Western blot, nor in intrinsic stability of the recombinant N-acetyltransferase protein. However, the G445A (Val149-->Ile) substitution yielded expression of recombinant NAT1 protein that catalyzed the N-acetylation of aromatic amines and the O- and N,O-acetylation of their N-hydroxylated metabolites at rates up to 2-fold higher than wild-type recombinant human NAT1.

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Nov 1, 1992·Environmental Health Perspectives·F F KadlubarN P Lang
Aug 3, 1988·Biochimica Et Biophysica Acta·D W Hein
Feb 1, 1995·Pharmacogenetics·K P VatsisM V Relling
Feb 15, 1993·Archives of Biochemistry and Biophysics·K P Vatsis, W W Weber
May 18, 1996·Lancet·I C Roberts-ThomsonR N Butler

❮ Previous
Next ❯

Citations

Feb 26, 2010·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Katy WalkerBabasaheb Sonawane
Nov 17, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Li JiaoDonghui Li
May 7, 1999·Environmental Health Perspectives·A Hirvonen
May 21, 1999·Drug Metabolism Reviews·I CascorbiI Roots
Feb 9, 2008·Drug Metabolism Reviews·Jason M WalravenDavid W Hein
Nov 1, 2005·Drug Metabolism Reviews·Sotiria Boukouvala, Giannoulis Fakis
Mar 26, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Azza M KamelHeba S Moussa
Jan 1, 1998·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·N IshibeK T Kelsey
Sep 18, 2018·Pharmacogenetics and Genomics·David W HeinSotiria Boukouvala
Jan 30, 2009·Environmental and Molecular Mutagenesis·Julia CatalánHannu Norppa
Mar 6, 2007·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Peter GresnerWojciech Wasowicz

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.