Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Cytochrome P450 in trypanosomatids

B J Berger1, A H Fairlamb

  • 1Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, U.K.

Biochemical Pharmacology
|July 6, 1993
PubMed
Summary

Trypanosomatids, including Trypanosoma brucei, possess cytochrome P450 enzymes catalyzing specific reactions. These enzymes, particularly active in T. cruzi epimastigotes, show distinct activities compared to mammalian systems.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Fexinidazole for the treatment of human African trypanosomiasis.

Drugs of today (Barcelona, Spain : 1998)·2019
Same author

Rational design of peptide-based inhibitors of trypanothione reductase as potential antitrypanosomal drugs.

Amino acids·2013
Same author

Machine vision applied to vehicle guidance.

IEEE transactions on pattern analysis and machine intelligence·2012
Same author

Increased levels of thiols protect antimony unresponsive Leishmania donovani field isolates against reactive oxygen species generated by trivalent antimony.

Parasitology·2007
Same author

Peptoid inhibition of trypanothione reductase as a potential antitrypanosomal and antileishmanial drug lead.

Amino acids·2002
Same author

Characterization of the ornithine aminotransferase from Plasmodium falciparum.

Molecular and biochemical parasitology·2001

Area of Science:

  • Biochemistry
  • Parasitology
  • Molecular Biology

Background:

  • Cytochrome P450 enzymes are crucial in drug metabolism and detoxification.
  • Trypanosomatids are protozoan parasites responsible for diseases like sleeping sickness and Chagas disease.
  • Understanding parasite enzyme systems can reveal potential drug targets.

Purpose of the Study:

  • To investigate the presence and activity of cytochrome P450-dependent reactions in various trypanosomatid species.
  • To characterize the substrate specificity and localization of these enzymatic activities.
  • To compare trypanosomatid cytochrome P450 activity with that of mammalian systems.

Main Methods:

  • Preparation of post-mitochondrial supernatant extracts from bloodstream forms of Trypanosoma brucei brucei, T. cruzi epimastigotes, Leishmania donovani promastigotes, and Crithidia fasciculata.
  • Assay of ethoxycoumarin deethylase and ethoxyresorufin deethylase activities.
  • Inhibition studies using cytochrome P450 inhibitors (carbon monoxide, proadifen, metyrapone).
  • Spectroscopic analysis (carbon monoxide difference spectra) to detect cytochrome P450.
  • Subcellular fractionation to determine enzyme localization.

Main Results:

  • All tested trypanosomatid extracts exhibited ethoxycoumarin deethylase and ethoxyresorufin deethylase activities, with T. cruzi epimastigotes showing the highest levels.
  • Enzymatic activities were inhibited by specific cytochrome P450 inhibitors, confirming their P450-dependence.
  • Unlike rat liver microsomes, no pentoxyresorufin depentylase or pentamidine hydroxylase activity was detected.
  • Carbon monoxide difference spectra indicated the presence of cytochrome P450 in C. fasciculata and T. b. brucei.
  • An additional hemoprotein absorbing at 420 nm was observed in C. fasciculata and T. b. brucei.
  • Ethoxycoumarin deethylase activity was primarily localized in the microsomal fraction of C. fasciculata.

Conclusions:

  • Trypanosomatids possess functional cytochrome P450 enzymes capable of specific metabolic reactions.
  • The enzymatic profile differs significantly from mammalian cytochrome P450 systems, suggesting potential for selective drug targeting.
  • Cytochrome P450 activity in C. fasciculata is predominantly associated with the microsomal fraction.

Related Experiment Videos