In vitro and in vivo characterization of retinoid synthesis from beta-carotene.
Retinoids are indispensable for the health of mammals, which cannot synthesize retinoids de novo. Retinoids are derived from dietary provitamin A carotenoids, like beta-carotene, through the actions of beta-carotene-15,15'-monooxygenase (BCMO1). As the substrates for retinoid-metabolizing enzymes are water insoluble, they must be transported intracellularly bound to cellular retinol-binding proteins. Our studies suggest that cellular retinol-binding protein, type I (RBP1) acts as an intracellular sensor of retinoid status that, when present as apo-RBP1, stimulates BCMO1 activity and the conversion of carotenoids to retinoids. Cellular retinol-binding protein, type II (RBP2), which is 56% identical to RBP1 does not influence BCMO1 activity. Studies of mice lacking BCMO1 demonstrate that BCMO1 is responsible for metabolically limiting the amount of intact beta-carotene that can be absorbed by mice from their diet. Our studies provide new insights into the regulation of BCMO1 activity and the physiological role of BCMO1 in living organisms.
Fierce
Yvette
Y
Department of Comparative Medicine, University of Washington, Raitt Hall 324, Seattle, WA 98195, USA.
de Morais Vieira
Milena
M
Piantedosi
Roseann
R
Wyss
Adrian
A
Blaner
William S
WS
Paik
Jisun
J
D000818:Animals; D016466:CHO Cells; D002338:Carotenoids / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular / Q000235:genetics / Q000378:metabolism*; D019207:beta Carotene / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics / Q000378:metabolism*
C518457:Rbp1 protein, mouse; C518461:Rbp2 protein, rat; D012176:Retinoids; D054840:Retinol-Binding Proteins, Cellular; D019207:beta Carotene; D002338:Carotenoids; D010088:Oxidoreductases; C422653:RDH11 protein, human; C493359:Bco1 protein, mouse; C493358:BCO1 protein, human; D050559:beta-Carotene 15,15'-Monooxygenase