Two carotenoid oxygenases contribute to Mammalian provitamin a metabolism

Jaume Amengual, M. Airanthi K. Widjaja-Adhi, Susana Rodriguez-Santiago, Susanne Hessel, Marcin Golczak, Krzysztof Palczewski, Johannes Von Lintig

Research output: Contribution to journalArticlepeer-review

Abstract

Mammalian genomes encode two provitamin A-converting enzymes as follows: the β-carotene-15, 15'-oxygenase (BCO1) and the β-carotene-9', 10'-oxygenase (BCO2). Symmetric cleavage by BCO1 yields retinoids (β-15'-apocarotenoids, C20), whereas eccentric cleavage by BCO2 produces long-chain (>C20) apocarotenoids. Here, we used genetic and biochemical approaches to clarify the contribution of these enzymes to provitamin A metabolism. We subjected wild type, Bco-/-, Bco2 -/-, and Bco1-/-Bco2-/-double knock-out mice to a controlled diet providing β-carotene as the sole source for apocarotenoid production. This study revealed that BCO1 is critical for retinoid homeostasis. Genetic disruption of BCO1 resulted in β-carotene accumulation and vitamin A deficiency accompanied by a BCO2-dependent production of minor amounts of β-apo-10'-carotenol (APO10ol). We found that APO10ol can be esterified and transported by the same proteins as vitamin A but with a lower affinity and slower reaction kinetics. In wild type mice, APO10ol was converted to retinoids by BCO1. We also show that a stepwise cleavage by BCO2 and BCO1 with APO10ol as an intermediate could provide a mechanism to tailor asymmetric carotenoids such as β-cryptoxanthin for vitamin A production. In conclusion, our study provides evidence that mammals employ both carotenoid oxygenases to synthesize retinoids from provitamin A carotenoids.

Original languageEnglish (US)
Pages (from-to)34081-34096
Number of pages16
JournalJournal of Biological Chemistry
Volume288
Issue number47
DOIs
StatePublished - Nov 22 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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