Retinol alternate pathways

Table I summarizes the FTCs for /3-carotene and retinol metabolism. Table I also summarizes the flow rates of /3-carotene and retinoid from donor to recipient compartments during steady state. As the mass of analyte in the system changes, the flows will also change, but the FTCs are expected to remain constant unless alternate pathways (mechanisms) for metabolism of the tracee are induced by the large dose of tracer.

Both RALDHl and RALDH2 also catalyze the conversion of 9-cw-retinal into 9-cis-RA [72, 73]. Therefore, they could also serve as partners with the ci s-retinoid RDH in a pathway that generates 9-cis-RA from 9-cw-retinol. Alternatively, they could catalyze synthesis of 9-cis-RA from 9-cw-retinal produced by central cleavage of 9-cw-p-carotene [74]. 

The central cleavage of P-carotene 1 is most likely the major pathway by which mammals produce the required retinoids il), in particular, retinal 2, which is essential for vision and is subsequently oxidized to retinoic acid 3 and reduced to retinol 4. An alternative excentric cleavage of 1 has been reported involving scission of the double bond at C7-C8 producing P-8 -apocarotenal 5 (2a,2b) which is subsequently oxidized to 2 (Fig. 1) (2c). The significance of carotene metabolites such as 2, 3 and 4 to embryonic development and other vital processes such as skin and membrane protection is a major concern of medicinal chemistry. 

Although it has been clearly demonstrated that under normal physiological conditions retinol absorption occurs mainly via the lymphatic route (see above Fidge et al., 1968), the existence of an alternative route for retinol absorption has been suggested both by experimental studies in the rat and by features of the genetic disease abetalipoproteinemia in man. Information available suggests that under abnormal conditions retinol may be able to be absorbed via a nonlymphatic pathway and in a biochemical form other than the chylomicron in amounts sufficient to meet nutritional requirements for vitamin A. 

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