Skip to main content
main-content

09.11.2018 | Original Article | Ausgabe 1/2019

Forensic Toxicology 1/2019

Metabolism of triacetone triperoxide (TATP) by canine cytochrome P450 2B11

Zeitschrift:
Forensic Toxicology > Ausgabe 1/2019
Autoren:
Kevin Colizza, Michelle Gonsalves, Lindsay McLennan, James L. Smith, Jimmie C. Oxley
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s11419-018-0450-9) contains supplementary material, which is available to authorized users.

Abstract

Purpose

This work is performed to determine if there is a potential for the accumulation and potential toxicity of triacetone triperoxide (TATP) in canines. Additional utility of this information may suggest human toxicity and possibly detection of biomarkers, metabolites or intact molecule of those using this material for nefarious reasons.

Methods

Liquid chromatography/mass spectrometry of dog liver microsome (DLM) incubation samples of TATP was used to measure substrate depletion. Trapping of electrophilic products was performed using glutathione (GSH) and semicarbazide. Comparisons were made to free hydroperoxides found in methyl ethyl ketone peroxides (MEKP).

Results

The non-specific Km value of 2.2 μM and a Vmax of 1.1 nmol/min/mg of protein were determined. Canine recombinant cytochrome P450 (rCYP) 2B11 with human cytochrome b5 was found to catalyze the NADPH-dependent metabolism of TATP into its only phase I metabolite, hydroxy-TATP (TATP-OH). No secondary metabolite(s) or degraded products were detected or trapped from microsomal incubations. MEKP subjected to similar conditions was found to undergo significant metabolism, semicarbazide trapping and rapid oxidation of GSH to GSSG. The synthesized TATP-OH metabolite incubated in DLM progressed three times faster than TATP metabolism with no secondary metabolites found or trapped.

Conclusions

TATP does not react as MEKP suggesting that TATP does not ring-open to form hydroperoxides. TATP and TATP-OH compete for the same enzyme, with TATP dominating this competition. Failure to detect additional metabolite(s) suggests they may be too small to detect by our system or bound covalently to a protein or polymer in the incubation reaction.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de. Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

Zusatzmaterial
Supplementary material 1 (PDF 531 kb)
11419_2018_450_MOESM1_ESM.pdf
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 1/2019

Forensic Toxicology 1/2019 Zur Ausgabe

Neu im Fachgebiet Rechtsmedizin

27.11.2018 | Hauptreferate: Tumorevolution II | Sonderheft 2/2018

Zirkulierende Tumorzellen beim Pankreaskarzinom

Ergebnisse morphologischer und molekularer Analysen und Vergleiche mit dem Primärtumor

23.11.2018 | Hauptreferate: Hauptprogramm der DGP | Sonderheft 2/2018

Das Urachuskarzinom – aktuelle Konzepte einer seltenen Tumorerkrankung

16.11.2018 | Hauptreferate: Hauptprogramm der DGP | Sonderheft 2/2018

Das Deutsche Mesotheliomregister

Aktuelle pathologische Diagnostik und Leistungen

14.11.2018 | Originalien | Ausgabe 6/2018

Retinale Blutungen beim Schütteltrauma

Differenzialdiagnostische Aspekte