A. During et al., beta-carotene 15,15 '-dioxygenase activity in human tissues and cells: evidence of an iron dependency, J NUTR BIOC, 12(11), 2001, pp. 640-647
The two objectives of this study were to investigate beta -carotene 15,15'-
dioxygenase activity in human tissues and to determine the effect of desfer
rioxamine on the dioxygenase activity. Two human in vitro models were used:
the TC7 clone of the intestinal cell line Caco-2 and small intestinal muco
sa preparations. beta -Carotene 15,15'-dioxygenase activity in the small in
testinal mucosa was (mean +/- SD) 97.4 +/- 39.8 pmol/h.mg protein for five
adults (44-89 y) and 20 pmol/h.mg for an infant (17 months). No activity wa
s detected in adult stomach tissue. We report for the first time the dioxyg
enase activity in human liver: 62 pmol/h.mg for a normal adult liver and 7
pmol/h.mg for a liver exhibiting gross pathology. The maximum capacity of b
eta -carotene cleavage in an adult was estimated to be 12 mg/day (one fifth
by small intestine and four fifths by liver), assuming an optimal beta -ca
rotene/retinal cleavage ratio of 1:2. The dioxygenase activity was decrease
d up to 80% with increasing desferrioxamine concentrations in the two in vi
tro models. Desferrioxamine was characterized as a noncompetitive inhibitor
. In TC7 cells, the inhibitory effect of desferrioxamine was reversed by ir
on addition, suggesting that this effect was related to the ability of desf
errioxamine to chelate iron, purported to be an obligate cofactor of the en
zyme. In conclusion, these data report the presence of beta -carotene 15,15
'-dioxygenase activity in human small intestine and liver and demonstrate t
hat desferrioxamine efficiently inhibits intestinal beta -carotene cleavage
in human tissues and cells. (C) 2001 Elsevier Science Inc. All rights rese
rved.