Carotene excentric cleavage

Wang X-D, Krinsky NI (1997) Identification and quantification of retinoic acid and other metabolites from P-carotene excentric cleavage in human intestine in vitro and ferret intestine in vivo. Methods Enzymol 282 117-130... 

Tibaduiza, E.C. et al., Excentric cleavage products of beta-carotene inhibit estrogen receptor positive and negative breast tumor cell growth in vitro and inhibit activator protein-1-mediated transcriptional activation, J. Nutr., 132, 1368, 2002. 

Tang, G. et al. (1991). Characterization of (3-apo-13 carotenone and (3-apo-14 -carotenal as enzymatic products of the excentric cleavage of (3-carotene. Biochemistry 30 9829-9834. 

Wang, X. D. et al. (1992). Retinoic acid can be produced from excentric cleavage of beta-carotene in human intestinal mucosa. Arch. Biochem. Biophys. 293(2) 298-304. 

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. 

The metabolism of (3-carotene (1) by central and by excentric cleavage to retinol (13) has been a topic of much debate [25]. Recently details of the central cleavage have been elegantly solved [27]. 

In second alternative excentric cleavage step of asymmetric cleavage, P-carotene (2) was converted to P-apo-lO -carotenal (23) and P-ionone (24) by P,P-carotene 9 ,10 -dioxygenase. These P-apo-carotenalscould be subsequently oxidized to the P-apo-carotenoic acids such as P-apo-10 -carotenoic acid (27) and P-apo-12 -carotenoic acid (28). Finally, these P-apo-carotenoic acids were further shortened to retinoic acid (20) (Figure 5). 

Figure 5. Each vitamin A biotransformation to retinoic acid (20) from provitamin A P-carotene (2) by both central cleavage enzyme P,P-carotene 15,15 -monooxygenase and alternative excentric cleavage enzyme P,P-carotene 9 ,10 -dioxygenase.

Figure 2. Metabolism of p-carotene to retinal via central cleavage and to retinoic acid via excentric cleavage.

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