Regulation of retinoic acid metabolism

RA metabolism is a critical mechanism in the local control of RA signaling. In developmental processes requiring RA, the balance between RA synthesis and RA catabolism is tightly controlled by the enzymes RALDH-2 and P450RAI, respectively. Also in the adult, the expression of these enzymes in tissues undergoing cell proliferation and differentiation, such as skin or tumor tissues, may have a direct influence on how they respond to endogenous or therapeutic doses of retinoids, in particular since it can be clearly demonstrated that in some cells and tissues, P450RAI/CYP26 expression is regulated by RA. The identification and characterization of P450RAI provides an important tool to examine the role that metabolism plays in directing RA signaling and a possible target for the design of novel therapeutics to enhance current retinoid therapies.