CYP26A1,B1,C1 4-hydroxylate atRA

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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).
Literature References
PubMed ID Title Journal Year
22019272 Craniosynostosis and multiple skeletal anomalies in humans and zebrafish result from a defect in the localized degradation of retinoic acid

Nikkels, PG, Breuning, MH, Kubisch, C, Pogoda, HM, Sutherland-Smith, AJ, Daniel, PB, Hammerschmidt, M, Bloch, W, Morgan, T, Robertson, SP, Wollnik, B, Rachwalski, M, van Haeringen, A, von Ameln, S, Laue, K, Alanay, Y, Sawyer, GM, Gray, MJ

Am. J. Hum. Genet. 2011
21529158 Cytochrome P450s in the regulation of cellular retinoic acid metabolism

Ross, AC, Zolfaghari, R

Annu. Rev. Nutr. 2011
14532297 A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis and all-trans isomers of retinoic acid

White, J, Taimi, M, Helvig, C, Petkovich, M, Ramshaw, H, Korczak, B, Amad, M, Wisniewski, J

J Biol Chem 2004
Catalyst Activity

retinoic acid 4-hydroxylase activity of CYP26A1,B1,C1 [endoplasmic reticulum membrane]

Orthologous Events
Cite Us!