Reaction: CYP26A1,B1,C1 4-hydroxylate atRA
- in pathway: RA biosynthesis pathway
All-trans-retinoic acid (atRA) is a biologically activated metabolite of vitamin A (retinol) and is essential for reproduction, embryonic development, growth, and multiple processes in the adult, including energy balance, neurogenesis, and the immune response. Cytochrome P450 26A1 and B1 (CYP26A1 and B1) play a key role in retinoid metabolism (Ross & Zolfaghari 2011). They 4-hydroxylate all-trans-retinoic acid (atRA), delivered by CRABP1, to form all-trans-4-hydroxyretinoic acid (4OH-atRA) which can then be eliminated from the body. CYP26A1 and B1 are also able to 4-hydroxylate 9-cis-retinoic acid and 13-cis-retinoic acid (9cRA and 13cRA respectively) in vitro. These enzymes are also produce 18-hydroxy and 4-oxo forms of these retinoic acids (not shown here).
The inactivation of RA by CYP26B1 is essential for postnatal survival and maintenance of the undifferentiated state of male germ cells during embryonic development in Sertoli cells. Excessive RA also has teratogenic effects in the limb and craniofacial skeleton. Defects in CYP26B1 can cause radiohumeral fusions with other skeletal and craniofacial anomalies (RHFCA; MIM:614416) (Laue et al. 2011).
The inactivation of RA by CYP26B1 is essential for postnatal survival and maintenance of the undifferentiated state of male germ cells during embryonic development in Sertoli cells. Excessive RA also has teratogenic effects in the limb and craniofacial skeleton. Defects in CYP26B1 can cause radiohumeral fusions with other skeletal and craniofacial anomalies (RHFCA; MIM:614416) (Laue et al. 2011).
Reaction - small molecule participants:
H2O [cytosol]
4OH-atRA [cytosol]
NADP+ [cytosol]
H+ [cytosol]
O2 [cytosol]
NADPH [cytosol]
Reactome.org reaction link: R-HSA-5362525
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Reaction input - small molecules:
hydron
dioxygen
NADPH(4-)
Reaction output - small molecules:
water
all-trans-4-hydroxyretinoic acid
NADP(3-)
Reactome.org link: R-HSA-5362525