Importance of β,β-carotene 15,15′-monooxygenase 1 (BCMO1) and β,β-carotene 9′,10′-dioxygenase 2 (BCDO2) in nutrition and health

In humans, varying amounts of absorbed beta-carotene are oxidatively cleaved by the enzyme beta,beta-carotene 15,15'-monooxygenase 1 (BCMO1) into two molecules of all-trans-retinal. The other carotenoid cleavage enzyme beta,beta-carotene 9',10'-dioxygenase (BCDO2) cleaves beta-carotene at the 9',10' double bond forming beta-apo-10'-carotenal and beta-ionone. Although the contribution of BCDO2 to vitamin A formation has long been debated, BCMO1 is currently considered the key enzyme for retinoid metabolism. Furthermore, BCMO1 has limited enzyme activity towards carotenoids other than provitamin A carotenoids, whereas BCDO2 exhibits a broader specificity. Both enzymes are located at different sites within the cell, with BCMO1 being a cytosolic protein and BCDO2 being located in the mitochondria. Expression of BCMO1 in tissues other than the intestine has recently revealed its function for tissue-specific retinoid metabolism with importance in embryogenesis and lipid metabolism. On the other hand, biological activity of BCDO2 metabolites has been shown to be important in protecting against carotenoid-induced mitochondrial dysfunction. Single-nucleotide polymorphisms (SNPs) such as R267S and A379V in BCMO1 can partly explain inter-individual variations observed in carotenoid metabolism. Advancing knowledge about the physiological role of these two enzymes will contribute to understanding the importance of carotenoids in health and disease.