Evidence map›Paper›PMID 33600157›Full record

ArticleACS chemical biology2021

The Structural and Biochemical Basis of Apocarotenoid Processing by β-Carotene Oxygenase-2.

Sepalika Bandara, Linda D Thomas, Srinivasagan Ramkumar, Nimesh Khadka, Philip D Kiser, Marcin Golczak, Johannes von Lintig

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Vitamin A supply in the eye and establishment of the visual cycle.Current topics in developmental biology · 2025
    Review
  5. Immunometabolic effects ofImmunometabolism (Cobham, Surrey) · 2024
    Review
  6. Review
  7. Carotenoids in Health as Studied by Omics-Related Endpoints.Advances in nutrition (Bethesda, Md.) · 2023
    Review
  8. Article
  9. Carotenoid enrichment in eggs: From biochemistry perspective.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2023
    Review
  10. Review
  11. Article
  12. Aster la vista: Unraveling the biochemical basis of carotenoid homeostasis in the human retina.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022
    Article
  13. Aster proteins mediate carotenoid transport in mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  14. Review
  15. Review
  16. Carotenoid modifying enzymes in metazoans.Methods in enzymology · 2022
    Article
  17. Article
  18. 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

7 authors at 2 institutions in 1 country.

Sepalika Bandara
Linda D Thomas
Srinivasagan Ramkumar
Nimesh Khadka
Philip D KiserDepartment of Physiology and Biophysics, University of California, Irvine, California 92697, United States.
Marcin Golczak
Johannes von LintigORCID 0000-0002-2079-2143
Case Western Reserve University · USUniversity of California, Irvine · US

Funding

TISSUE CULTURE AND HYBRIDOMA MODULEP30EY011373 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Irina A Pikuleva · 1997 to 2026
$17.7M
VISUAL SCIENCES TRAINING PROGRAMT32EY007157 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Johannes Friedrich von Lintig · 2000 to 2026
$5.5M
Carotinoids in VisionR01EY020551 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI VON LINTIG, JOHANNES FRIEDRICH · 2011 to 2024
$4.8M
STRA6 and Ocular Vitamin A HomeostasisR01EY028121 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI Johannes Friedrich von Lintig · 2018 to 2026
$4.3M
Regulation of vitamin A metabolism in the eyeR01EY023948 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI GOLCZAK, MARCIN BERNARD · 2014 to 2023
$3.8M
Retinoid cycles and retinal disease treatmentI01BX004939 · VA · VETERANS HEALTH ADMINISTRATION · PI KISER, PHILIP DAVID · 2020 to 2025
–
BLRD VA I01 BX004939NEI NIH HHS P30 EY011373NEI NIH HHS R01 EY020551NEI NIH HHS R01 EY023948NEI NIH HHS R01 EY028121NEI NIH HHS T32 EY007157
6 · The paper itself

Abstract

In mammals, carotenoids are converted by two carotenoid cleavage oxygenases into apocarotenoids, including vitamin A. Although knowledge about β-carotene oxygenase-1 (BCO1) and vitamin A metabolism has tremendously increased, the function of β-carotene oxygenase-2 (BCO2) remains less well-defined. We here studied the role of BCO2 in the metabolism of long chain β-apocarotenoids, which recently emerged as putative regulatory molecules in mammalian biology. We showed that recombinant murine BCO2 converted the alcohol, aldehyde, and carboxylic acid of a β-apocarotenoid substrate by oxidative cleavage at position C9,C10 into a β-ionone and a diapocarotenoid product. Chain length variation (C20 to C40) and ionone ring site modifications of the apocarotenoid substrate did not impede catalytic activity or alter the regioselectivity of the double bond cleavage by BCO2. Isotope labeling experiments revealed that the double bond cleavage of an apocarotenoid followed a dioxygenase reaction mechanism. Structural modeling and site directed mutagenesis identified amino acid residues in the substrate tunnel of BCO2 that are critical for apocarotenoid binding and catalytic processing. Mice deficient for BCO2 accumulated apocarotenoids in their livers, indicating that the enzyme engages in apocarotenoid metabolism. Together, our study provides novel structural and functional insights into BCO2 catalysis and establishes the enzyme as a key component of apocarotenoid homeostasis in mice.

Indexed as

AlcoholsAldehydesbeta CaroteneCarboxylic AcidsCarotenoidsCatalysisCloning, MolecularDioxygenasesEscherichia coliIsotope LabelingLipid MetabolismModels, MolecularMolecular StructureOxidative StressOxygenasesOxygen IsotopesAlcoholsAldehydesBco2 protein, mousebeta CaroteneCarboxylic Acidscarotenoid oxygenaseCarotenoidsDioxygenasesOxygen-18OxygenasesOxygen IsotopesVitamin A

Identifiers

PMID33600157
PMCPMC8082539
OpenAlexW3130377659

What OpenQuestion holds

Textmetadata
LicenceTDM
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.