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Enzyme Research
Volume 2012 (2012), Article ID 416062, 7 pages
http://dx.doi.org/10.1155/2012/416062
Research Article

Inhibition of Heme Peroxidases by Melamine

Division of Biochemical Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA

Received 23 March 2012; Revised 23 May 2012; Accepted 5 June 2012

Academic Editor: Fabrizio Briganti

Copyright © 2012 Pattaraporn Vanachayangkul and William H. Tolleson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In 2008 melamine-contaminated infant formula and dairy products in China led to over 50,000 hospitalizations of children due to renal injuries. In North America during 2007 and in Asia during 2004, melamine-contaminated pet food products resulted in numerous pet deaths due to renal failure. Animal studies have confirmed the potent renal toxicity of melamine combined with cyanuric acid. We showed previously that the solubility of melamine cyanurate is low at physiologic pH and ionic strength, provoking us to speculate how toxic levels of these compounds could be transported through the circulation without crystallizing until passing into the renal filtrate. We hypothesized that melamine might be sequestered by heme proteins, which could interfere with heme enzyme activity. Four heme peroxidase enzymes were selected for study: horseradish peroxidase (HRP), lactoperoxidase (LPO), and cyclooxygenase-1 and -2 (COX-1 and -2). Melamine exhibited noncompetitive inhibition of HRP ( 𝐾 𝑖 9 . 5 Β± 0 . 7 m M ) , and LPO showed a mixed model of inhibition ( 𝐾 𝑖 1 4 . 5 Β± 4 . 7 m M ) . The inhibition of HRP and LPO was confirmed using a chemiluminescent peroxidase assay. Melamine also exhibited COX-1 inhibition, but inhibition of COX-2 was not detected. Thus, our results demonstrate that melamine inhibits the activity of three heme peroxidases.