Evidence map›Paper›PMID 23703616›Full record

ArticleThe Journal of biological chemistry2013

The involvement of mitochondrial amidoxime reducing components 1 and 2 and mitochondrial cytochrome b5 in N-reductive metabolism in human cells.

Birte Plitzko, Gudrun Ott, Debora Reichmann, Colin J Henderson, C Roland Wolf, Ralf Mendel, Florian Bittner, Bernd Clement, Antje Havemeyer

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. The History of mARC.Molecules (Basel, Switzerland) · 2023
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. [Non-antagonistic influence of Krumeich's intrastromal corneal ring in an experimental tissue culture system].Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft · 2016
    Article
  14. Review
  15. Article
  16. The mammalian molybdenum enzymes of mARC.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2015
    Review
  17. Nitrite reduction by molybdoenzymes: a new class of nitric oxide-forming nitrite reductases.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2015
    Review
  18. The biosynthesis of the molybdenum cofactors.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2015
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Birte PlitzkoDepartment of Pharmaceutical and Medicinal Chemistry, Pharmaceutical Institute, Christian-Albrechts-University of Kiel, 24118 Kiel, Germany.
Gudrun Ott
Debora Reichmann
Colin J Henderson
C Roland Wolf
Ralf Mendel
Florian Bittner
Bernd Clement
Antje Havemeyer
Kiel University · DETechnische Universität Braunschweig · DEUniversity of Dundee · GB

Funding

Cancer Research UK 10822
6 · The paper itself

Abstract

The mitochondrial amidoxime reducing component mARC is a recently discovered molybdenum enzyme in mammals. mARC is not active as a standalone protein, but together with the electron transport proteins NADH-cytochrome b5 reductase (CYB5R) and cytochrome b5 (CYB5), it catalyzes the reduction of N-hydroxylated compounds such as amidoximes. The mARC-containing enzyme system is therefore considered to be responsible for the activation of amidoxime prodrugs. All hitherto analyzed mammalian genomes code for two mARC genes (also referred to as MOSC1 and MOSC2), which share high sequence similarities. By RNAi experiments in two different human cell lines, we demonstrate for the first time that both mARC proteins are capable of reducing N-hydroxylated substrates in cell metabolism. The extent of involvement is highly dependent on the expression level of the particular mARC protein. Furthermore, the mitochondrial isoform of CYB5 (CYB5B) is clearly identified as an essential component of the mARC-containing N-reductase system in human cells. The participation of the microsomal isoform (CYB5A) in N-reduction could be excluded by siRNA-mediated down-regulation in HEK-293 cells and knock-out in mice. Using heme-free apo-CYB5, the contribution of mitochondrial CYB5 to N-reductive catalysis was proven to strictly depend on heme. Finally, we created recombinant CYB5B variants corresponding to four nonsynonymous single nucleotide polymorphisms (SNPs). Investigated mutations of the heme protein seemed to have no significant impact on N-reductive activity of the reconstituted enzyme system.

Indexed as

AnimalsBlotting, WesternCell Line, TumorCytochrome-B(5) ReductaseCytochromes b5HEK293 CellsHumansMembrane ProteinsMiceMice, KnockoutMitochondriaMitochondrial ProteinsMolybdenumMutationOxidation-ReductionOxidoreductasesAmidoxamidoxime reducing component, humanCytochrome-B(5) ReductaseCytochromes b5Membrane ProteinsMitochondrial ProteinsMolybdenumMTARC2 protein, humanOxidoreductasesOximesProtein IsoformsCYB5BDrug MetabolismHememARCMitochondriaMolybdenumMOSCN-reductionRNA Interference (RNAi)

Identifiers

PMID23703616
PMCPMC3711290
OpenAlexW1998576933

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.