Fig. 2

Generic retinoid pathway (not taking into account of tissue specificities, see text for details). Retinol is stored in cells (mainly liver stellate cells) in the form of fatty acid esters. Its secretion in the bloodstream as retinol bind to the plasma retinol binding protein (RBP4) is tightly regulated so that the serum concentration in humans is constantly in the 2 μM range. Retinol can be reversibly metabolised to retinal via RDHs. Retinal can also be oxidised to retinoic acid, the most active form of vitamin A via ligation to retinoid receptors RARs and RXRs. RXRs can interact as an heterodimer with many other nuclear receptors and regulate gene expression. β-carotene can be a source of retinal via centric cleavage by BCMO1. An alternative pathway has been proposed which would involve eccentric cleavage of β-carotene by BCDO2 (releasing β-apo-10′-carotenal) as the initial step. β-apo-14′-carotenal, retinal, and retinoic acid have been shown to modulate nuclear receptor activity, sometimes in an opposite manner. BCDO2 β-carotene 9′,10′-dioxygenase, BCMO1 β-carotene 15,15′-monooxygenase, FXR farnesoid X receptor, RAR retinoic acid receptor, RXR retinoid X receptor, LXR liver X receptor, TR thyroid hormone receptor, PPAR peroxisome proliferator-activated receptor, ?: unidentified protein(s)