Evidence map›Paper›PMID 34949674›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2022

Interindividual Variability and Differential Tissue Abundance of Mitochondrial Amidoxime Reducing Component Enzymes in Humans.

Deepak Ahire, Abdul Basit, Lisa J Christopher, Ramaswamy Iyer, J Steven Leeder, Bhagwat Prasad

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. mARC1 Is the Main Contributor to Metabolic Reduction ofJournal of medicinal chemistry · 2024
    Article
  2. Review
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

6 authors at 1 institution in 2 countries.

Deepak AhireDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (D.A., A.B., B.P.); Department of Nonclinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, New Jersey (L.J.C., R.I.); and Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L.).ORCID 0000-0001-8537-6047
Abdul BasitDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (D.A., A.B., B.P.); Department of Nonclinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, New Jersey (L.J.C., R.I.); and Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L.).
Lisa J ChristopherDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (D.A., A.B., B.P.); Department of Nonclinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, New Jersey (L.J.C., R.I.); and Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L.).
Ramaswamy IyerDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (D.A., A.B., B.P.); Department of Nonclinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, New Jersey (L.J.C., R.I.); and Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L.).
J Steven LeederDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (D.A., A.B., B.P.); Department of Nonclinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, New Jersey (L.J.C., R.I.); and Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L.).
Bhagwat PrasadDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (D.A., A.B., B.P.); Department of Nonclinical Disposition and Bioanalysis, Bristol Myers Squibb, Princeton, New Jersey (L.J.C., R.I.); and Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri (J.S.L.) bhagwat.prasad@wsu.edu.ORCID 0000-0001-6688-0504
Children's Mercy Hospital · US

Funding

PBPK prediction of ontogeny mediated alteration in hepatic drug eliminationR01HD081299 · NICHD · WASHINGTON STATE UNIVERSITY · PI PRASAD, BHAGWAT · 2015 to 2025
$4.6M
NICHD NIH HHS HHSN275200900011CNICHD NIH HHS R01 HD081299
6 · The paper itself

Abstract

Mitochondrial amidoxime-reducing component (mARC) enzymes are molybdenum-containing proteins that metabolize a number of endobiotics and xenobiotics. The interindividual variability and differential tissue abundance of mARC1 and mARC2 were quantified using targeted proteomics in three types of tissue fractions: 1) pediatric liver tissue homogenates, 2) total membrane fraction of the paired liver and kidney samples from pediatric and adult donors, and 3) pooled S9 fractions of the liver, intestine, kidney, lung, and heart. The absolute levels of mARC1 and mARC2 in the pediatric liver homogenate were 40.08 ± 4.26 and 24.58 ± 4.02 pmol/mg homogenate protein, respectively, and were independent of age and sex. In the total membrane fraction of the paired liver and kidney samples, the abundance of hepatic mARC1 and mARC2 was comparable, whereas mARC2 abundance in the kidney was approximately 9-fold higher in comparison with mARC1. The analysis of the third set of samples (i.e., S9 fraction) revealed that mARC1 abundance in the kidney, intestine, and lung was 5- to 13-fold lower than the liver S9 abundance, whereas mARC2 abundance was approximately 3- and 16-fold lower in the intestine and lung than the liver S9, respectively. In contrast, the kidney mARC2 abundance in the S9 fraction was approximately 2.5-fold higher as compared with the hepatic mARC2 abundance. The abundance of mARC enzymes in the heart was below the limit of quantification (∼0.6 pmol/mg protein). The mARC enzyme abundance data presented here can be used to develop physiologically based pharmacokinetic models for the prediction of in vivo pharmacokinetics of mARC substrates. SIGNIFICANCE STATEMENT: A precise targeted quantitative proteomics method was developed and applied to quantify newly discovered drug-metabolizing enzymes, mARC1 and mARC2, in pediatric and adult tissue samples. The data suggest that mARC enzymes are ubiquitously expressed in an isoform-specific manner in the human liver, kidney, intestine, and lung, and the enzyme abundance is not associated with age and sex. These data are important for developing physiologically based pharmacokinetic models for the prediction of in vivo pharmacokinetics of mARC substrates.

Indexed as

Mitochondrial ProteinsOximesAdultChildHumansLiverOxidoreductasesamidoximeMitochondrial ProteinsOxidoreductasesOximes

Identifiers

PMID34949674
PMCPMC8969132
OpenAlexW4200052263

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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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.