| First Author | Amengual J | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 47 | Pages | 34081-96 |
| PubMed ID | 24106281 | Mgi Jnum | J:204979 |
| Mgi Id | MGI:5543838 | Doi | 10.1074/jbc.M113.501049 |
| Citation | Amengual J, et al. (2013) Two carotenoid oxygenases contribute to mammalian provitamin A metabolism. J Biol Chem 288(47):34081-96 |
| abstractText | Mammalian genomes encode two provitamin A-converting enzymes as follows: the beta-carotene-15,15'-oxygenase (BCO1) and the beta-carotene-9',10'-oxygenase (BCO2). Symmetric cleavage by BCO1 yields retinoids (beta-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, Bco1(-/-), Bco2(-/-), and Bco1(-/-)Bco2(-/-) double knock-out mice to a controlled diet providing beta-carotene as the sole source for apocarotenoid production. This study revealed that BCO1 is critical for retinoid homeostasis. Genetic disruption of BCO1 resulted in beta-carotene accumulation and vitamin A deficiency accompanied by a BCO2-dependent production of minor amounts of beta-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 beta-cryptoxanthin for vitamin A production. In conclusion, our study provides evidence that mammals employ both carotenoid oxygenases to synthesize retinoids from provitamin A carotenoids. |
