Arylamine N-acetyltransferases*

Sim, E.; Fullam, E.; Wakefield, L.

doi:10.1016/b978-0-08-046884-6.00419-x

Cited by 7 publications

(11 citation statements)

References 191 publications

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“…Finally, our in vivo studies in mice deficient or heterozygous for mouse Nat1 (the mouse ortholog of human NAT2) (21,31) affirm that decreased Nat1 levels increased fasting glucose, insulin, and TG levels. Even more compelling are the data from the GTTs and ITTs, showing that loss of Nat1 results in an IR phenotype.…”

Section: Discussionmentioning

confidence: 89%

“…Interestingly, the rapid acetylator genotype was associated with lower skin fluorescence but higher fasting glucose and HbA1C values. While the crystal structure of NAT2 has been resolved in complex with CoA, neither K268R (rs1208) nor I114T (rs1801280) are known to play a direct role in these interactions, but several of the coding SNPs, including rs1801280, are thought to increase protein degradation (31,45,46), thereby affecting the acetylator phenotype.…”

Section: Discussionmentioning

confidence: 99%

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Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene

Knowles¹,

Xie²,

Zhang³

et al. 2015

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene

Knowles¹,

Xie²,

Zhang³

et al. 2015

J. Clin. Invest.

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“…Arylamine N-acetyltransferases (NATs) are classically known as drug metabolizing enzymes and are amenable to assay in vitro through their ability to metabolize arylamines, hydrazines, and alkylarylamines (Sim et al, 2007). This acetylation reaction can lead either to detoxification (mainly by Nacetylation) or to bioactivation (mainly by O-acetylation) and DNA adduct formation, implicating NATs in modulating susceptibility, for example, to bladder or prostate cancer (Hein, 2002).…”

Section: Introductionmentioning

confidence: 99%

Arylamine N‐acetyltransferase 1 expression in breast cancer cell lines: A potential marker in estrogen receptor‐positive tumors

Wakefield

Robinson

Long

et al. 2007

Genes Chromosomes & Cancer

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The prognosis for patients with estrogen receptor (ER)-positive breast cancer has improved significantly with the prescription of selective ER modulators (SERMs) for ER-positive breast cancer treatment. However, only a proportion of ER-positive tumors respond to SERMs, and resistance to hormonal therapies is still a major problem. Detailed analysis of published microarray studies revealed a positive correlation between overexpression of the drug metabolizing enzyme arylamine N-acetyltransferase type 1 (NAT1) and ER positivity, and increasing evidence supports a biological role for NAT1 in breast cancer progression. We have tested a range of ER-positive and ER-negative breast cancer cell lines for NAT1 enzyme activity, and monitored promoter and polyadenylation site usage. Amongst ER-positive lines, NAT1 activities ranged from 202 +/- 28 nmol/min/mg cellular protein (ZR-75-1) to 1.8 +/- 0.4 nmol/min/mg cellular protein (MCF-7). The highest levels of NAT1 activity could not be attributed to increased NAT1 gene copy number; however, we did detect differences in NAT1 promoter and polyadenylation site usage amongst the breast tumor-derived lines. Thus, whilst all cell lines tested accumulated transcripts derived from the proximal promoter, the line expressing NAT1 most highly additionally initiated transcripts initiating at a more distal, "tissue"-specific promoter. These data pave the way for investigating NAT1 transcripts as candidate prognostic markers in ER-positive breast cancer.

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“…NAT metabolize several drugs, such as sulfonamides and isoniazid. 26 In the rat, similar to human, there are two isoforms (Nat1 and Nat2), although a third isoform (Nat3) with less metabolic activity was recently characterized. 27 The objectives of this study were to determine the effects of CRF on hepatic NAT and to define the mechanisms leading to their downregulation.…”

mentioning

confidence: 99%

“…26 These enzymes are expressed in the liver; they catalyze acetyl group transfer from acetyl-CoA to an aromatic or heterocyclic amine, hydrazine, hydrazide, or N-hydroxylamine acceptor substrate. NAT metabolize several drugs, such as sulfonamides and isoniazid.…”

mentioning

confidence: 99%

Downregulation of Hepatic Acetylation of Drugs in Chronic Renal Failure

Simard¹,

Naud²,

Jl³

et al. 2008

Journal of the American Society of Nephrology

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Drug metabolism can be affected by chronic renal failure (CRF). Although it is known that several drugs that are known to be acetylated accumulate in CRF, the effect of CRF on N-acetyltransferase (NAT), the enzyme responsible for this acetylation, is unknown. Herein is reported that protein and gene expression of both Nat isoforms in the liver was reduced by Ͼ30% and Nat2 activity was reduced by 50% in rats with CRF compared with control rats. Incubation of hepatocytes with serum from rats with CRF suggested that a circulating factor is responsible for the decrease in protein and gene expression. For testing the hypothesis that parathyroid hormone may be this factor, CRF was induced in parathyroidectomized rats; downregulation of Nat expression and activity was not observed in these rats. Furthermore, addition of parathyroid hormone to cultured hepatocytes induced a decrease in Nat2 protein and gene expression. In conclusion, liver acetylation of drugs in a rat model of CRF is reduced by a downregulation of Nat1 and Nat2 isoforms, secondary to decreased gene expression. Parathyroid hormone seems to be an important mediator of this phenomenon.

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Arylamine N-acetyltransferases*

Cited by 7 publications

References 191 publications

Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene

Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene

Arylamine N‐acetyltransferase 1 expression in breast cancer cell lines: A potential marker in estrogen receptor‐positive tumors

Downregulation of Hepatic Acetylation of Drugs in Chronic Renal Failure

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