ArticleThe Journal of biological chemistry2010
Molecular identification of NAT8 as the enzyme that acetylates cysteine S-conjugates to mercapturic acids.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 73 citations in OpenAlex.
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- Evaluation of PE5 Entries on the Human Proteome Project Target List.Journal of proteome research · 2025Article
- Plasma and Urine Metabolites Associated With Nondiabetic Chronic Kidney Disease: The HELIUS Study.Kidney medicine · 2025Article
- Polymorphic pseudogenes in the human genome - a comprehensive assessment.Human genetics · 2024Article
- Huppke-Brendel syndrome: Novel cases and a therapeutic trial with ketogenic diet and N-acetylcysteine.JIMD reports · 2024Article
- Genetic variants affecting mitochondrial function provide further insights for kidney disease.BMC genomics · 2024Article
- The desert woodrat (Neotoma lepida) induces a diversity of biotransformation genes in response to creosote bush resin.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2024Article
- Role of Transporters and Enzymes in Metabolism and Distribution of 4-Chlorokynurenine (AV-101).Molecular pharmaceutics · 2024Article
- Microbiota-gut-liver-brain axis and hepatic encephalopathy.Microbiome research reports · 2024Review
- A metabolomics study in aqueous humor discloses altered arginine metabolism in Parkinson's disease.Fluids and barriers of the CNS · 2023Article
- The Key Role of GSH in Keeping the Redox Balance in Mammalian Cells: Mechanisms and Significance of GSH in Detoxification via Formation of Conjugates.Antioxidants (Basel, Switzerland) · 2023Review
- Genetic studies of paired metabolomes reveal enzymatic and transport processes at the interface of plasma and urine.Nature genetics · 2023Article
- Causal effects of human serum metabolites on occurrence and progress indicators of chronic kidney disease: a two-sample Mendelian randomization study.Frontiers in nutrition · 2023Article
- Biogenic Amine Levels Markedly Increase in the Aqueous Humor of Individuals with Controlled Type 2 Diabetes.International journal of molecular sciences · 2022Article
- Article
- Squalene synthase predicts poor prognosis in stage I-III colon adenocarcinoma and synergizes squalene epoxidase to promote tumor progression.Cancer science · 2022Article
- Cysteine as a Multifaceted Player in Kidney, theMolecules (Basel, Switzerland) · 2022Review
- Endoplasmic reticulum acetyltransferases Atase1 and Atase2 differentially regulate reticulophagy, macroautophagy and cellular acetyl-CoA metabolism.Communications biology · 2021Article
- Rare genetic variants affecting urine metabolite levels link population variation to inborn errors of metabolism.Nature communications · 2021Article
- Article
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Authors and funding
6 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our goal was to identify the reaction catalyzed by NAT8 (N-acetyltransferase 8), a putative N-acetyltransferase homologous to the enzyme (NAT8L) that produces N-acetylaspartate in brain. The almost exclusive expression of NAT8 in kidney and liver and its predicted association with the endoplasmic reticulum suggested that it was cysteinyl-S-conjugate N-acetyltransferase, the microsomal enzyme that catalyzes the last step of mercapturic acid formation. In agreement, HEK293T extracts of cells overexpressing NAT8 catalyzed the N-acetylation of S-benzyl-L-cysteine and leukotriene E(4), two cysteine conjugates, but were inactive on other physiological amines or amino acids. Confocal microscopy indicated that NAT8 was associated with the endoplasmic reticulum. Neither of the two frequent single nucleotide polymorphisms found in NAT8, E104K nor F143S, changed the enzymatic activity or the expression of the protein by >or=2-fold, whereas a mutation (R149K) replacing an extremely conserved arginine suppressed the activity. Sequencing of genomic DNA and EST clones corresponding to the NAT8B gene, which resulted from duplication of the NAT8 gene in the primate lineage, disclosed the systematic presence of a premature stop codon at codon 16. Furthermore, truncated NAT8B and NAT8 proteins starting from the following methionine (Met-25) showed no cysteinyl-S-conjugate N-acetyltransferase activity when transfected in HEK293T cells. Taken together, these findings indicate that NAT8 is involved in mercapturic acid formation and confirm that NAT8B is an inactive gene in humans. NAT8 homologues are found in all vertebrate genomes, where they are often encoded by multiple, tandemly repeated genes as many other genes encoding xenobiotic metabolism enzymes.
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