Arylamine N-acetyltransferases 2

Published on October 1, 2007 Updated on July 28, 2016   23 min

Other Talks in the Series: Drug Metabolizing Enzymes

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Arylamine N-acetyltransferases. Part 2 I'm Edith Sim and I've been working on these enzymes for over 20 years.
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So human NAT1 is a phase II drug-metabolizing enzyme. It's over 80% identical to human NAT2. It's widespread tissue distribution. It is also subject to genetic polymorphism. And the genetic polymorphism, like in human NAT2, appears in many instances and result in the protein being degraded within cells, therefore, being unavailable to carrier deacetylation. Human NAT1 has got a different substrate specificity then human NAT2. It N-acetylates, para-aminobenzoic acid and para-aminosalicylate. It's expressed early in development, unlike human NAT2. It is overexpressed in ER positive breast cancer. And recently it's also been demonstrated that it hydrolyses acetylCoA in the presence of folate.
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The evolution of a tree of NATs in primates, although all of these enzymes are very similar, clearly divides into three groups. The NAT1s, the NAT2s, and the NAT pseudo genes. Therefore, this suggests that the duplication of these loci occurred prior to the break time or the development of the different strands of the primate derivatives.