Evidence map›Paper›PMID 40618281›Full record

ArticleHuman molecular genetics2025

Metabolic rerouting of valine and isoleucine oxidation increases survival in zebrafish models of disorders of propionyl-CoA metabolism.

Sungkook Hong, Joel Pardo, PamelaSara E Head, Katharine T Ellis, Madeline L Arnold, Nathan P Achilly, Blake Carrington, Kevin Bishop, Raman Sood, Lisa Kratz and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. 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

13 authors.

Sungkook HongNational Human Genome Research Institute, NIH, Bethesda, MD, 10 Center Drive Building 10, Room 7S257 Bethesda, MD 20892, United States.
Joel PardoNational Human Genome Research Institute, NIH, Bethesda, MD, 10 Center Drive Building 10, Room 7S257 Bethesda, MD 20892, United States.
PamelaSara E HeadNational Human Genome Research Institute, NIH, Bethesda, MD, 10 Center Drive Building 10, Room 7S257 Bethesda, MD 20892, United States.
Katharine T EllisNational Human Genome Research Institute, NIH, Bethesda, MD, 10 Center Drive Building 10, Room 7S257 Bethesda, MD 20892, United States.
Madeline L ArnoldNational Human Genome Research Institute, NIH, Bethesda, MD, 10 Center Drive Building 10, Room 7S257 Bethesda, MD 20892, United States.
Nathan P AchillyNational Human Genome Research Institute, NIH, Bethesda, MD, 10 Center Drive Building 10, Room 7S257 Bethesda, MD 20892, United States.
Blake CarringtonNational Human Genome Research Institute, Zebrafish Core, NIH, Building 6, Bethesda, MD 20892, United States.
Kevin BishopNational Human Genome Research Institute, Zebrafish Core, NIH, Building 6, Bethesda, MD 20892, United States.
Raman SoodNational Human Genome Research Institute, Zebrafish Core, NIH, Building 6, Bethesda, MD 20892, United States.
Lisa KratzBiochemical Genetics Laboratory, The Kennedy Krieger Institute, 707 North Broadway, Baltimore, MD 21205, United States.
Jennifer L SloanNational Human Genome Research Institute, NIH, Bethesda, MD, 10 Center Drive Building 10, Room 7S257 Bethesda, MD 20892, United States.
Oleg A ShchelochkovNational Human Genome Research Institute, NIH, Bethesda, MD, 10 Center Drive Building 10, Room 7S257 Bethesda, MD 20892, United States.
Charles P VendittiNational Human Genome Research Institute, NIH, Bethesda, MD, 10 Center Drive Building 10, Room 7S257 Bethesda, MD 20892, United States.

Funding

Investigations of Methylmalonic Acidemia and Related DisordersZIAHG200318 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI VENDITTI, CHARLES P · 2009 to 2025
$29.7M
Intramural NIH HHS ZIA HG200318Intramural Research Program of the National Human Genome Research Institute 1ZIAHG200318-21Organic Acidemia AssociationPropionic Acidemia Foundation
6 · The paper itself

Abstract

Branched-chain amino acid (BCAA) oxidation is a multistep process leading to the formation of acetyl-CoA and propionyl-CoA. The syndromes associated with disturbed BCAA oxidation are clinically and biochemically heterogenous. While the common organic acidemias, propionic (PA) and methylmalonic acidemia (MMA), arise from deficient activity of propionyl-CoA carboxylase and methylmalonyl-CoA mutase and are life-threatening conditions with limited treatment options, isobutyryl-CoA dehydrogenase (IBD), and 2-methylbutyryl-CoA dehydrogenase (2-MBD) deficiencies manifest as biochemical traits, with no associated symptoms or consistent metabolic phenotypes. To assess whether the proximal interruption of valine and isoleucine oxidation might represent an approach to treat MMA and PA, we investigated the effects of loss of function of acad8 (encoding IBD) and acadsb (encoding 2-MBD), singly and doubly, on biochemical and morphological findings of zebrafish models of pccb-related propionic acidemia (PA) and mmut methylmalonic acidemia (MMA). Although acad8-/-;acadsb-/- double mutants showed growth failure and early mortality, the proximal interruption of valine and isoleucine oxidation in double (pccb/acad8, pccb/acadsb, mmut/acad8, mmut/acadsb) and triple (pccb/acad8/acadsb, mmut/acad8/acadsb) homozygous mutants improved pccb-/- and mmut-/- survival and reduced propionate-derived toxic metabolites, supporting the rationale for pursuing modulation of IBD and 2-MBD activity as a strategy to reduce the metabolic load and improve clinical outcomes in PA and MMA.

Indexed as

Acyl Coenzyme AAmino Acid Metabolism, Inborn ErrorsIsoleucinePropionic AcidemiaValineAcyl-CoA DehydrogenaseAnimalsDisease Models, AnimalHumansMethylmalonyl-CoA MutaseOxidation-ReductionPropionatesZebrafishZebrafish ProteinsAcyl-CoA DehydrogenaseAcyl Coenzyme AIsoleucineMethylmalonyl-CoA MutasePropionatespropionyl-coenzyme AValineZebrafish ProteinsBCAA oxidationmetabolic reroutingmethylmalonic acidemiapropionic acidemiazebrafish

Identifiers

PMID40618281
PMCPMC12371525

What Socratic 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 Socratic graph.