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

exploration of retinoic acid metabolism (Marill et al. 2003). Although the metabolism of
retinoic acid plays a crucial role in the functioning of this molecule, the specific
metabolic pathways and a number of its metabolites still remain to be identified.
Another enigma of retinoic acid metabolism is retinoic acid's potential to covalently bind
and retinoylate a number of intracellular proteins. Retynoilation is a process of posttranslation
modification of proteins by covalently binding retinoic acid (retinoic acid
acylation)(Almagor and Bar-Tana 1990; Takahashi et al. 1989; Takahashi and Breitman
1990; Takahashi and Breitman 1989; Tournier et al. 1996). This post-translation
modification of proteins results in a change in the physiological and chemical properties
of target proteins thus effecting their addressing and targeting characteristics (Marill et al.
2003). Another effect of this process is the utilization of free retinoic acid, which may
decrease the amount of active signaling molecules, thereby affecting the signaling
properties of these retinoids. The retynoilation of proteins also explains the effects of
some synthetic retinoids. Through the process of retynoilation, synthetic retinoids can
exhibit their therapeutic effects without the activation of retinoic acid intranuclear
receptors.
IV.b.l.Retinoic acid synthesis: The liver is considered to be a major sight for synthesis
of retinoic acid. Hepatocytes are found to be rich in cytosolic and membrane bound
enzymes that catalyse the oxidation of retinol to its aldehyde metabolite- retinal(Blaner
WS and Olson JA 1994). This reversible reaction is considered to be a rate limiting step
in the metabolism of all of the retinoid family members including retinoic acid. The
conversion of retinol to retinal is achieved through the action of retinol dehydrogenase
group (RDH) of enzl.rnes, which consists of three enzymatic systems: short chain
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