Fig. 2

Biosynthesis and clearance pathway of all-trans retinoic acid (at-RA). a Retinol (vitamin A) complexes with cellular retinol binding proteins (CRBP) for intracellular transport. The first stage of at-RA synthesis is the conversion of retinol to retinaldehyde via the oxidative capacity of retinol dehydrogenase (RDH) family enzymes. Retinaldehyde reductases (RALR) can reverse this process as a rate limiting step in at-RA production and reduce retinaldehyde back to retinol. Finally, retinaldehyde is oxidised to at-RA upon the activity of retinaldehyde dehydrogenases (RALDH) and binds to its own cellular transport protein (CRABP). b Once synthesised at-RA may signal in an autocrine or paracrine manner. CYP26 family enzymes can deactivate at-RA by catabolism into less bioactive compounds including 4-oxo retinoic acid and 18-hydroxy retinoic acid. This acts as a regulator of at-RA abundance and is important for maintenance of cellular homoeostasis