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. Author manuscript; available in PMC: 2021 Nov 12.
Published in final edited form as: Reprod Toxicol. 2020 Jun 13;96:102–113. doi: 10.1016/j.reprotox.2020.06.007

Figure 1. Retinoic acid metabolism.

Figure 1.

The availability of RA is tightly controlled in the mammalian CNS. Mammals are unable to synthesize RA de novo and require intake of vitamin A or other precursors (β-carotenes) from food sources. Vitamin A is converted to retinaldehyde by alcohol dehydrogenases (ADHs) and retinol dehydrogenases (RDHs). In mouse, RDH10 is necessary for conversion of retinol to retinaldehyde in the developing embryo [38]. Enzymes such as Short-chain Dehydrogenase/Reductase 3 (DHRS3) facilitates the reverse transformation of retinaldehyde to retinol [40, 68]. Retinaldehyde is further oxidized to form RA by aldehyde dehydrogenases (ALDHs or RALDHs) in an irreversible step. RALDH2 is critical for RA synthesis during early CNS development [42]. Cytochrome p450 26 subfamily enzymes regulate RA levels in the embryo and catalyze reactions to reduce RA bioavailability by converting RA to 4-OH-RA, 4-oxo RA, and other oxidized, less active metabolites [43]. These metabolites undergo glucuronidation which promote elimination pathways [180].