Evidence map›Paper›PMID 29883100›Full record

ArticleACS chemical biology2018

The Biochemical Basis of Vitamin A Production from the Asymmetric Carotenoid β-Cryptoxanthin.

Mary E Kelly, Srinivasagan Ramkumar, Weizhong Sun, Crystal Colon Ortiz, Philip D Kiser, Marcin Golczak, Johannes von Lintig

Abstract read
In one paragraph

Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

48 citing papers in PubMed, 72 citations in OpenAlex.

  1. Review
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  6. Recent advances in carotenoid absorption, distribution, and elimination.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025
    Review
  7. Article
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  10. Vitamin A supply in the eye and establishment of the visual cycle.Current topics in developmental biology · 2025
    Review
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  12. Immunometabolic effects ofImmunometabolism (Cobham, Surrey) · 2024
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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 1 institution in 1 country.

Mary E KellyDepartment of Pharmacology , Case Western Reserve University School of Medicine , Cleveland , Ohio 44106 , United States.
Srinivasagan RamkumarDepartment of Pharmacology , Case Western Reserve University School of Medicine , Cleveland , Ohio 44106 , United States.
Weizhong SunDepartment of Pharmacology , Case Western Reserve University School of Medicine , Cleveland , Ohio 44106 , United States.
Crystal Colon OrtizDepartment of Pharmacology , Case Western Reserve University School of Medicine , Cleveland , Ohio 44106 , United States.
Philip D KiserDepartment of Pharmacology , Case Western Reserve University School of Medicine , Cleveland , Ohio 44106 , United States.ORCID 0000-0003-1184-9539
Marcin GolczakDepartment of Pharmacology , Case Western Reserve University School of Medicine , Cleveland , Ohio 44106 , United States.
Johannes von LintigDepartment of Pharmacology , Case Western Reserve University School of Medicine , Cleveland , Ohio 44106 , United States.ORCID 0000-0002-2079-2143
University School · US

Funding

STRUCTURAL STUDIES OF ARRESTINSR01EY009339 · NEI · UNIVERSITY OF WASHINGTON · PI KISER, PHILIP DAVID, PALCZEWSKI, KRZYSZTOF · 1992 to 2025
$16.0M
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
Regulation of vitamin A metabolism in the eyeR01EY023948 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI GOLCZAK, MARCIN BERNARD · 2014 to 2023
$3.8M
Studies on visual cycles and their relevance to age-related macular degenerationIK2BX002683 · VA · VETERANS HEALTH ADMINISTRATION · PI KISER, PHILIP DAVID · 2015 to 2019
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BLRD VA IK2 BX002683NEI NIH HHS R01 EY009339NEI NIH HHS R01 EY020551NEI NIH HHS R01 EY023948NEI NIH HHS T32 EY007157
6 · The paper itself

Abstract

Vitamin A serves essential functions in mammalian biology as a signaling molecule and chromophore. This lipid can be synthesized from more than 50 putative dietary provitamin A precursor molecules which contain at least one unsubstituted β-ionone ring. We here scrutinized the enzymatic properties and substrate specificities of the two structurally related carotenoid cleavage dioxygenases (CCDs) which catalyze this synthesis. Recombinant BCO1 split substrates across the C15,C15' double bond adjacent to a canonical β-ionone ring site to vitamin A aldehyde. Substitution of the ring with a hydroxyl group prevented this conversion. The removal of methyl groups from the polyene carbon backbone of the substrate did not impede enzyme activity. Homology modeling and site-directed mutagenesis identified amino acid residues at the entrance of the substrate tunnel, which determined BCO1's specificity for the canonical β-ionone ring site. In contrast, BCO2 split substrates across the C9,C10 double bond adjacent to assorted ionone ring sites. Kinetic analysis revealed a higher catalytic efficiency of BCO2 with substrates bearing 3-hydroxy-β-ionone rings. In the mouse intestine, the asymmetric carotenoid β-cryptoxanthin with one canonical and one 3-hydroxy-β-ionone ring site was meticulously converted to vitamin A. The tailoring of this asymmetric substrate occurred by a stepwise processing of the carotenoid substrate by both CCDs and involved a β-apo-10'-carotenal intermediate. Thus, opposite selectivity for ionone ring sites of the two mammalian CCDs complement each other in the metabolic challenge of vitamin A production from a chemically diverse set of precursor molecules.

Indexed as

Animalsbeta-Carotene 15,15'-MonooxygenaseBeta-CryptoxanthinDioxygenasesHumansMiceModels, MolecularSubstrate SpecificityVitamin ABCO2 protein, humanBco2 protein, mousebeta-Carotene 15,15'-MonooxygenaseBeta-CryptoxanthinDioxygenasesVitamin A

Identifiers

PMID29883100
PMCPMC6158786
OpenAlexW2806766499

What OpenQuestion holds

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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.