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The Biochemical Basis of Vitamin A Production from the Asymmetric Carotenoid β-Cryptoxanthin
Open accessAbstract
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.
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There are more than 50 provitamin A carotenoids, but only β-carotene, α-carotene, and β-cryptoxanthin are present in significant amounts in the human diet.
“There are more than 50 provitamin A carotenoids, but only β-carotene, α-carotene, and β-cryptoxanthin are present in significant amounts in the human diet [9].”
From Vitamin A Update: Forms, Sources, Kinetics, Detection, Function, Deficiency, Therapeutic Use and Toxicity (2021) · cites this paper as [9]
The paper’s Abstract (page unavailable) says that about 50 food carotenoids have provitamin A activity and names β-carotene, α-carotene, and β-cryptoxanthin as examples. It does not say there are more than 50, or that only those three occur in significant amounts in the human diet. (LLM, conf=0.88)
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Carazo, A., Macáková, K., Matoušová, K., Krčmová, L. K., Protti, M., & Mladěnka, P. (2021) · Nutrients · doi:10.3390/nu13051703 · Cited by 461
Metadata
- Authors
- Kelly, M. E., Ramkumar, S., Sun, W., Colon Ortiz, C., Kiser, P. D., Golczak, M., & von Lintig, J.
- Affiliations
- Case Western Reserve University (US)
- Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, United States
- Venue
- ACS Chemical Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-06-08
- Volume
- 13
- Issue
- 8
- Pages
- 2121-2129
- ISSN
- 1554-8929 (ISSN-L)
- 1554-8937
- PMC
- PMC6158786
- OpenAlex
- W2806766499
- Cited by
- 74
- References
- 38
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 6 · 2023: 9 · 2022: 15 · 2021: 6 · 2020: 9 · 2019: 11 · 2018: 1
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- ACS Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (EY020551)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant biochemistry and biosynthesis
- Keywords
- vitamin A biosynthesis, beta-cryptoxanthin, carotenoid cleavage dioxygenase, BCO1, BCO2, beta-ionone ring, substrate specificity, mouse intestine, carotenoid cleavage, vitamin A aldehyde
- MeSH terms
- Beta-Cryptoxanthin, Animals, Humans, Models, Molecular, Substrate Specificity, Vitamin A, Dioxygenases, beta-Carotene 15,15'-Monooxygenase, Mice
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