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il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...

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etinal intermedi<strong>at</strong>es and directly metabolizes beta-carotene into a 15,15'-enediol before<br />

it is cleaved to c<strong>at</strong>echol and uitim<strong>at</strong>ely to cis-cis mucinoic acid (Napoli and Race 1988)'<br />

The cis-cis mucinoic acid <strong>the</strong>n converts to retinoic acid through an unknown mechanism.<br />

The study performed by V/ang et al. (1991) has shown th<strong>at</strong> <strong>the</strong> incub<strong>at</strong>ion <strong>of</strong> liver, lung,<br />

kidney and f<strong>at</strong> homogen<strong>at</strong>es from several animals with beta carotene has resulted in <strong>the</strong><br />

form<strong>at</strong>ion <strong>of</strong> retinoic acid without a change in retinal levels. This indic<strong>at</strong>es th<strong>at</strong> retinoic<br />

acid syn<strong>the</strong>sis from beta carotene is not achieved through <strong>the</strong> retinal intermedi<strong>at</strong>e (Wang<br />

et al. 1991). Although <strong>the</strong> complex process <strong>of</strong> retinoic acid is currently widely explored,<br />

<strong>the</strong> exact sights <strong>of</strong> syn<strong>the</strong>sis and enzymes involved in this process still remain to be<br />

discovered.<br />

IV.b.2.Retinoic acid transport: Retinoic acid is transported in plasma bound to albumin<br />

(Blaner WS and Olson JA 1994). The fasting plasma levels <strong>of</strong> retinoic acid are generally<br />

very low (1-14 nmoVl-) and represent 0.2-0.7 o/o <strong>of</strong> all <strong>of</strong> retinol plasma levels (Arnold et<br />

aI. 1996; De Leenheer et al. 1982; Eckh<strong>of</strong>f and Nau 1990). The concentr<strong>at</strong>ion <strong>of</strong> retinoic<br />

acid in plasma <strong>of</strong> animals such as r<strong>at</strong> was found to be even lower l-7 nmoVL (Cullum<br />

andZlle 1985; Napoli et al. 1985). The concentr<strong>at</strong>ion <strong>of</strong> retinoic acid inplasma canbe<br />

significantly altered by a dietary intake <strong>of</strong> vitamin A and its precursors. However, <strong>the</strong><br />

high fractional c<strong>at</strong>abolic r<strong>at</strong>e <strong>of</strong> retinoic acid (30.4 plasma pools/hr) indic<strong>at</strong>es th<strong>at</strong> plasma<br />

levels <strong>of</strong> retinoic acid may be strictly maintained, despite an increased intake (Eckh<strong>of</strong>f et<br />

al. 1991). It is thought th<strong>at</strong> <strong>the</strong> most <strong>of</strong> retinoic acid is derived from retinol which is taken<br />

by ,cells through <strong>the</strong> cellular membrane. The role <strong>of</strong> plasma RBP is still deb<strong>at</strong>able,<br />

however <strong>the</strong> current hypo<strong>the</strong>sis is th<strong>at</strong> <strong>the</strong>re is a possibility <strong>of</strong> an existence <strong>of</strong> specific<br />

RBP receptors on cellular membrane th<strong>at</strong> facilit<strong>at</strong>e trans-membrane transport <strong>of</strong> retinol<br />

38

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