Retinoid metabolism: new insights.

Vitamin A (retinol) is a critical micronutrient required for the control of stem cell functions, cell differentiation, and cell metabolism in many different cell types, both during embryogenesis and in the adult organism. However, we must obtain vitamin A from food sources. Thus, the uptake and metabolism of vitamin A by intestinal epithelial cells, the storage of vitamin A in the liver, and the metabolism of vitamin A in target cells to more biologically active metabolites, such as retinoic acid (RA) and 4-oxo-RA, must be precisely regulated. Here, I will discuss the enzymes that metabolize vitamin A to RA and the cytochrome P450 Cyp26 family of enzymes that further oxidize RA. Because much progress has been made in understanding the regulation of ALDH1a2 (RALDH2) actions in the intestine, one focus of this review is on the metabolism of vitamin A in intestinal epithelial cells and dendritic cells. Another focus is on recent data that 4-oxo-RA is a ligand required for the maintenance of hematopoietic stem cell dormancy and the important role of RARβ (RARB) in these stem cells. Despite this progress, many questions remain in this research area, which links vitamin A metabolism to nutrition, immune functions, developmental biology, and nuclear receptor pharmacology.