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Identification of Mycobacterium tuberculosis enzyme involved in vitamin D and 7-dehydrocholesterol metabolism

A V Vasilevskaya1, A V Yantsevich1, G V Sergeev1

  • 1Institute of Bioorganic Chemistry, National Academy of Sciences, 220141, Minsk, Kuprevicha 5/2, Belarus.

The Journal of Steroid Biochemistry and Molecular Biology
|June 12, 2016
PubMed

Insights

Researchers discovered that Mycobacterium tuberculosis cytochrome P450 124 (MTCYP124) can metabolize vitamin D3. This finding suggests a potential new drug target for tuberculosis treatment by exploring alternative vitamin D3 metabolic pathways.

Area of Science:

  • Biochemistry
  • Microbiology
  • Drug Discovery

Background:

  • Tuberculosis treatment challenges necessitate research into Mycobacterium drug molecular targets.
  • Cytochrome P450 enzymes are crucial for metabolizing biologically significant molecules.
  • Mycobacterium tuberculosis CYP124 (MTCYP124) is known to hydroxylate methyl-branched lipids.

Purpose of the Study:

  • To investigate the potential of MTCYP124 as a drug target.
  • To explore the substrate specificity of MTCYP124 beyond lipid hydroxylation.
  • To determine if MTCYP124 interacts with provitamin D3 and vitamin D3.

Main Methods:

  • Enzymatic assays using purified MTCYP124.
  • Incubation of MTCYP124 with provitamin D3 and vitamin D3.
  • Analysis of reaction products using analytical techniques.

Main Results:

  • MTCYP124 was found to oxidize both provitamin D3 and vitamin D3.
  • The resulting oxidation products were identified as distinct from known vitamin D3 metabolites (1α- and 25-hydroxyvitamin D3).

Conclusions:

  • MTCYP124 exhibits a novel enzymatic activity towards vitamin D3.
  • This suggests MTCYP124 may play a role in an alternative vitamin D3 metabolism pathway.
  • MTCYP124 represents a potential novel drug target for tuberculosis therapy.
Keywords:
7-DehydrocholesterolCytochrome P450Steroid metabolismVitamin D

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