Metabolic activation of glutamic acid pyrolysis products, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole and 2-amino-dipyrido[1,2-a:3',2'-d]imidazole, by purified cytochrome P-450

Chemico-biological Interactions
K IshiiR Kato

Abstract

Metabolic activation by cytochrome P-450 of glutamic acid pyrolysis products, 2-amino-6-methyldipyrido(1,2-a:3',2'-d)imidazole (Glu-P-1) and 2-amino-dipyrido(1,2,-a:3',2'-d)imidazole (Glu-P-2), to mutagenic metabolites was studied using Salmonella typhimurium TA98 as a tester strain. Cytochrome P-450, NADPH-cytochrome P-450 reductase and NADPH were essential requirements for the activation of these compounds. Of the four forms of cytochrome P-450 examined, polychlorinated biphenyls (PCB) P-448 and 3-methylcholanthrene (MC) P-448 purified from liver microsomes of rats treated with a PCB mixture and MC, respectively, showed high activity in the activation of both Glu-P-1 and Glu-P-2. The presence of three metabolites from Glu-P-1 or Glu-P-2 was demonstrated by high performance liquid chromatographic (HPLC) analysis. Among the metabolites of Glu-P-1, two metabolites were mutagenic without any further enzymatic activation. In accordance with the results of a mutation assay, PCB P-448 also exhibited higher activity to form the major mutagenic metabolite of Glu-P-1. The major active metabolite of Glu-P-1 was characterized as N-hydroxy-Glu-P-1 by chemical analysis using oxidizing and reducing reagents and by mass spectrometry.

Citations

Jan 1, 1987·Archives of Toxicology·D V Parke
Apr 1, 1988·Mutation Research·C de MeesterG Saint-Ruf
Jul 1, 1985·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·D J LouryJ L Byard
Nov 1, 1988·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·G M AlinkJ H Koeman
Dec 1, 1993·The Journal of Steroid Biochemistry and Molecular Biology·M WarnerJ A Gustafsson
Mar 11, 2000·Drug Metabolism Reviews·R Kato, Y Yamazoe
Jul 1, 1986·Biochemical Pharmacology·D F LewisD V Parke
Jul 1, 1984·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Y YamazoeR Kato
Jul 29, 1983·Biochemical and Biophysical Research Communications·M NagaoT Sugimura
Sep 1, 1988·Human Toxicology·D V ParkeD F Lewis
Aug 1, 1986·Environmental Health Perspectives·S SatoT Sugimura
Mar 1, 1983·Environmental Health Perspectives·R KatoY Yamazoe
Apr 1, 1985·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·K SaitoR Kato
Jul 14, 2017·Journal of Molecular Recognition : JMR·Ambareesh Kumar Singh, Meenakshi Singh
Jan 1, 1985·Environmental Mutagenesis·L L Vuolo, G J Schuessler
Jan 1, 1984·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·C IoannidesD V Parke

Related Concepts

Glu-P-1
Glu-P-2, monohydrobromide
Metazoa
Metabolic Biotransformation
Cytochrome P-450 Oxygenase
Glutamic Acids
Hot Temperature
Imidazoles
Microsomes, Liver
Mutagenicity Tests

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

The Tendon Seed Network

Tendons are rich in the extracellular matrix and are abundant throughout the body providing essential roles including structure and mobility. The transcriptome of tendons is being compiled to understand the micro-anatomical functioning of tendons. Discover the latest research pertaining to the Tendon Seed Network here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Incretins

Incretins are metabolic hormones that stimulate a decrease in glucose levels in the blood and they have been implicated in glycemic regulation in the remission phase of type 1 diabetes. Here is the latest research.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Long COVID-19

“Long Covid-19” describes illness in patients who are reporting long-lasting effects of the SARS-CoV-19 infection, often long after they have recovered from acute Covid-19. Ongoing health issues often reported include low exercise tolerance and breathing difficulties, chronic tiredness, and mental health problems such as post-traumatic stress disorder and depression. This feed follows the latest research into Long Covid.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.