In enterocytes, the dominant retinol-binding protein is RBP2 (CRBPII) which is abundant and binds retinol faster than the cell membrane. So, even though lipophilic retinol can easily enter the cell membrane of bowel enterocytes, it is collected by the abundancy of RBP2 into the enterocyte cytosol where it is further processed (Inagami & Ong 1997).

In enterocytes, all-trans-retinal (atRAL) binds to RBP2 (CRBPII) for stabilisation, metabolism and transport (Fierce et al. 2008).

Although the enzyme catalysing retinal reduction in human enterocytes is not identified, the best candidate is retinol dehydrogenase 11 (RDH11, RalR1). It is expressed in the intestine, has a basic pH optimum, and localises to the ER membrane where LRAT catalyses the next step in the pathway. However, RDH11 catalyses retinal reduction to retinol in vitro and uses NADPH as cofactor (Fierce et al. 2008).

RDH11 is the best-characterised enzyme that reduces all-trans-retinal (atRAL) to all-trans-retinol (atROL). In addition, several aldo-keto reductase (AKR) enzymes from subfamilies 1B and 1C also show all-trans-retinal (atRAL) reductase activity. AKR1B10 shows high reductase activity towards atRAL (Gallego et al. 2007, Ruiz et al. 2009) whereas AKR1C1, 1C3 and 1C4 all show much lower reductase activity towards arRAL (Ruiz et al. 2011).

Transfer of fatty acyl residues (FACYLs) from lecithin is the main way to esterify all-trans-retinol (atROL). Lecithin is a generic name for the yellowy-brown fatty substances in animals and tissues. It can be composed of phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols. Fatty acyl transfer is catalyzed by Lecithin retinol acyltransferase (LRAT) and takes place near the endoplasmic reticulum membrane. The main fatty acyl moieties that are substrates for LRAT are palmitoyl, oleoyl, stearoyl and linoleoyl groups present in the A1 position of membrane phosphatidylcholine molecules. LRAT esterifies atROL with these acyl groups to form all-trans-retinyl esters (atREs). The aim is not storage but transport via chylomicrons (Ruiz et al. 1999).

All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC containing demethylases are able to demethylate tri , di and monomethylated lysines. KDM5A-D (JARID1A-D) catalyse the demethylation of di- or tri-methylated lysine-5 of histone H3 (H3K4Me2/3) (Christensen et al. 2007, Klose et al. 2007, Lee et al. 2007, Secombe et al. 2007, Seward et al. 2007, Iwase et al. 2007).

All characterized lysine demethylases other than KDM1A belong to the jumonjiC domain (JmjC) containing family.The JmjC KDMs are members of the Cupin superfamily of mononuclear Fe (II) dependent oxygenases, which are characterized by the presence of a double-stranded beta-helix core fold. The JmjC KDMs require 2 oxoglutarate (2 OG) and molecular oxygen as co substrates, producing, along with formaldehyde, succinate and carbon dioxide. This hydroxylation based mechanism does not require a protonatable lysine epsilon-amine group and consequently JmjC containing demethylases are able to demethylate tri , di and monomethylated lysines. KDM5A-D (JARID1A-D) catalyse the demethylation of di- or tri-methylated lysine-5 of histone H3 (H3K4Me2/3) (Christensen et al. 2007, Klose et al. 2007, Lee et al. 2007, Secombe et al. 2007, Seward et al. 2007, Iwase et al. 2007).