Reactome | Signaling by Retinoic Acid

Signaling by Retinoic Acid

Stable Identifier

R-HSA-5362517

DOI

10.3180/REACT_267785.1

Type

Pathway

Species

Homo sapiens

ReviewStatus

4/5

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Vitamin A (retinol) can be metabolised into active retinoid metabolites that function either as a chromophore in vision or in regulating gene expression transcriptionally and post-transcriptionally. Genes regulated by retinoids are essential for reproduction, embryonic development, growth, and multiple processes in the adult, including energy balance, neurogenesis, and the immune response. The retinoid used as a cofactor in the visual cycle is 11-cis-retinal (11cRAL). The non-visual cycle effects of retinol are mediated by retinoic acid (RA), generated by two-step conversion from retinol (Napoli 2012). All-trans-retinoic acid (atRA) is the major activated metabolite of retinol. An isomer, 9-cis-retinoic acid (9cRA) has biological activity, but has not been detected in vivo, except in the pancreas. An alternative route involves BCO1 cleavage of carotenoids into retinal, which is then reduced into retinol in the intestine (Harrison 2012). The two isomers of RA serve as ligands for retinoic acid receptors (RAR) that regulate gene expression. (Das et al. 2014). RA is catabolised to oxidised metabolites such as 4-hydroxy-, 18-hydroxy- or 4-oxo-RA by CYP family enzymes, these metabolites then becoming substrates for Phase II conjugation enzymes (Ross & Zolfaghari 2011).

Literature References

PubMed ID	Title	Journal	Year
24393720	Retinoic acid signaling pathways in development and diseases Karki, R, Torregroza, I, Mahapatra, S, Kambhampati, S, Das, S, Evans, T, Thapa, P, Das, BC, Verma, A, Wallace, DP, Ray, SK, Van Veldhuizen, P, Liu, TC	Bioorg. Med. Chem.	2014
21529158	Cytochrome P450s in the regulation of cellular retinoic acid metabolism Ross, AC, Zolfaghari, R	Annu. Rev. Nutr.	2011
21621639	Physiological insights into all-trans-retinoic acid biosynthesis Napoli, JL	Biochim. Biophys. Acta	2012
21718801	Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids Harrison, EH	Biochim. Biophys. Acta	2012