Retinoic acid can be produced from excentric cleavage of beta-carotene in human intestinal mucosa.
The hypothesis that retinoic acid (RA) is produced from the excentric cleavage of beta-carotene was tested in human intestinal homogenates in vitro. Significant amounts of RA were identified by HPLC and derivatization after incubation of intestinal mucosal homogenates with retinal, beta-carotene, or beta-apocarotenals at 37 degrees C for 60 min. RA formation was inhibited, in a dose-dependent fashion, when retinal was incubated in the presence of 0.1-3.0 mM citral (3,7-dimethyl-2,6-octadienal) under identical experimental conditions. The formation of RA from both beta-carotene and beta-apocarotenals was dose and time dependent and RA was the major metabolite of both beta-apo-8'-carotenal and beta-apo-12'-carotenal after the incubation. However, citral (0.1 to 4 mM) did not inhibit the formation of beta-apocarotenals and RA from 2 microM beta-carotene (P greater than 0.05), which proves the existence of an excentric cleavage mechanism for beta-carotene conversion into retinoids. Furthermore, RA formation from both beta-apo-8'-carotenal and beta-apo-12'-carotenal in human intestinal homogenate occurred in the presence of citral, which demonstrates that RA can be produced from excentric cleavage of beta-carotene via a series of beta-apocarotenals as intermediates.
Wang
X D
XD
Gastrointestinal Nutrition Laboratory, USDA Human Nutrition Research Center, Boston, Massachusetts.
Krinsky
N I
NI
Tang
G W
GW
Russell
R M
RM
D000080462:Acyclic Monoterpenes; D001667:Binding, Competitive; D002338:Carotenoids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism*; D039821:Monoterpenes; D013729:Terpenes / Q000494:pharmacology; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D019207:beta Carotene
D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D013729:Terpenes; D019207:beta Carotene; D002338:Carotenoids; D014212:Tretinoin; C007076:citral