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NAT— from bugs to brains An overview of the 2nd International Workshop on the arylamine N-acetyltransferases

The Pharmacogenomics Journal volume 2, pages 152–155 (2002)Cite this article

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The arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes responsible for the biotrans- formation of various arylamine and heterocyclic amines, including drugs and carcinogenic compounds. Genes encoding NAT and NAT-like genes have been identified in several vertebrate and eubacterial species.1,2 In humans, genetically determined inter-individual variation in NAT2 protein content is the basis of the well-known isoniazid acetylation polymorphism, which has significant toxicological implications.3 The second International Workshop on the arylamine N-acetyltransferases was held in Eynsham Hall, near Oxford, UK, on October 5–6, 2001. This meeting was organized by Edith Sim (Oxford University) in consultation with Rod Minchin (University of Western Australia) and David Hein (University of Louisville). The purpose of this meeting was to present and discuss the most recent developments in the study of arylamine N-acetyltransferases. The symposium dealt with molecular biology, genetic, and biochemical aspects and also included clinically oriented presentations. The presentations were organized into four sessions dealing with the endogenous and developmental roles of NAT, the detection of NAT polymorphisms and their association with disease, the control of NAT gene expression, and NAT structure and enzymology. The oral and poster presentations demonstrated major advances in the field and provided a forum for scientists to discuss their work, facilitating the setting up of new collaborative projects.

The first theme provided early debate with groups from Tucson (Robert Erickson, Department of Pediatrics, University of Arizona Health Sciences, USA) and Oxford (Katalin Pinter and Valerie Cornish, Department of Pharma- cology, Oxford University, UK). It has been proposed that murine NAT2 and human NAT1 play similar roles in folate catabolism through the acetylation of the catabolite folate para-aminobenzoylglutamate. However, Robert Erickson presented data obtained with mouse red blood cells which show that increased NAT activity does not correlate with an enhanced catabolite flow from the folate pool. Katalyn Pinter and Valerie Cornish described effects of transgenic expression of human NAT1 and NAT2 knock-out mice which indicate that overexpression is more detrimental to the developing embryos than the knock-out. The physiological effect of varying NAT expression on folate metabolism needs further work but intriguing studies suggesting a relationship with the splotch mouse which causes neural tube defects was presented by Lesley Stanley's group (Sarah Windridge, De Montfort University, UK). This theme was continued in a presentation by David Iovannisci (Children's Hospital Oakland Research Institute, Canada) who described an association of NAT*10 with cleft lip and palate in a large human population.

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References

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Acknowledgements

The meeting was sponsored by The Wellcome Trust, Roche, The Cancer Research Campaign, The International Society for the Study of Xenobiotics, Waters, the Oxfordshire Golf Club, Blackwell Science, Promega and Oxford University Press. We also acknowledge James Sandy for his help in the organisation of this meeting.

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Authors and Affiliations

  1. CNRS-UMR7000, Faculté de Médecine Pitié-Salpêtrière, Paris and UFR de Biochimie, Université Denis Diderot-Paris, Paris 7, France

    F Rodrigues-Lima & J-M Dupret

  2. Department of Dermatology, University Hospital Aachen, Rhein Wesfal TH Aachen, Aachen, Germany

    B Blömeke

  3. Department of Pharmacology, Oxford University, Oxford, UK

    E Sim

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  1. F Rodrigues-Lima
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  2. B Blömeke
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  3. E Sim
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  4. J-M Dupret
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Correspondence to J-M Dupret.

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Rodrigues-Lima, F., Blömeke, B., Sim, E. et al. NAT— from bugs to brains An overview of the 2nd International Workshop on the arylamine N-acetyltransferases. Pharmacogenomics J 2, 152–155 (2002). https://doi.org/10.1038/sj.tpj.6500114

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