Editing Vitamin A (section)

===Fetal alcohol spectrum disorder===
[[Fetal alcohol spectrum disorder]] (FASD), formerly referred to as fetal alcohol syndrome, presents as craniofacial malformations, neurobehavioral disorders and mental disabilities, all attributed to exposing human embryos to alcohol during fetal development.<ref name="Fainsod2020"/><ref name="Petrelli2019"/> The risk of FASD depends on the amount consumed, the frequency of consumption, and the points in pregnancy at which the alcohol is consumed.<ref>{{cite web|title=Fetal Alcohol Exposure |url=http://pubs.niaaa.nih.gov/publications/FASDFactsheet/FASDfact.htm|access-date=16 December 2021|date=April 2015|url-status=live|archive-url=https://web.archive.org/web/20150610050738/http://pubs.niaaa.nih.gov/publications/FASDFactsheet/FASDfact.htm|archive-date=10 June 2015}}</ref> [[Ethanol]] is a known [[teratogen]], i.e., causes birth defects. Ethanol is metabolized by [[alcohol dehydrogenase]] enzymes into [[acetaldehyde]].<ref name="Farrés">{{cite journal | vauthors = Farrés J, Moreno A, Crosas B, Peralba JM, Allali-Hassani A, Hjelmqvist L, Jörnvall H, Parés X | title = Alcohol dehydrogenase of class IV (sigma sigma-ADH) from human stomach. cDNA sequence and structure/function relationships | journal = European Journal of Biochemistry | volume = 224 | issue = 2 | pages = 549–57 | date = September 1994 | pmid = 7925371 | doi = 10.1111/j.1432-1033.1994.00549.x | doi-access = free | title-link = doi }}</ref><ref>{{cite journal | vauthors = Edenberg HJ, McClintick JN | title = Alcohol Dehydrogenases, Aldehyde Dehydrogenases, and Alcohol Use Disorders: A Critical Review | journal = Alcoholism: Clinical and Experimental Research | volume = 42 | issue = 12 | pages = 2281–97 | date = December 2018 | pmid = 30320893 | pmc = 6286250 | doi = 10.1111/acer.13904 }}</ref> The subsequent oxidation of acetaldehyde into acetate is performed by [[aldehyde dehydrogenase]] enzymes. Given that retinoic acid (RA) regulates numerous embryonic and differentiation processes, one of the proposed mechanisms for the teratogenic effects of ethanol is a competition for the enzymes required for the biosynthesis of RA from vitamin A. Animal research demonstrates that in the embryo, the competition takes place between acetaldehyde and retinaldehyde for aldehyde dehydrogenase activity. In this model, acetaldehyde inhibits the production of retinoic acid by retinaldehyde dehydrogenase. Ethanol-induced developmental defects can be ameliorated by increasing the levels of retinol, retinaldehyde, or retinaldehyde dehydrogenase. Thus, animal research supports the reduction of retinoic acid activity as an [[etiological]] trigger in the induction of FASD.<ref name="Fainsod2020">{{cite book |vauthors=Fainsod A, Bendelac-Kapon L, Shabtai Y |title=The Biochemistry of Retinoid Signaling III |chapter=Fetal Alcohol Spectrum Disorder: Embryogenesis Under Reduced Retinoic Acid Signaling Conditions |series=Subcellular Biochemistry |volume=95 |pages=197–225 |date=2020 |pmid=32297301 |doi=10.1007/978-3-030-42282-0_8|isbn=978-3-030-42280-6 |s2cid=215793789 }}</ref><ref name="Petrelli2019">{{cite journal | vauthors = Petrelli B, Bendelac L, Hicks GG, Fainsod A | title = Insights into retinoic acid deficiency and the induction of craniofacial malformations and microcephaly in fetal alcohol spectrum disorder | journal = Genesis | volume = 57 | issue = 1 | pages = e23278 | date = January 2019 | pmid = 30614633 | doi = 10.1002/dvg.23278 | s2cid = 58603210 }}</ref><ref name="Shabtai2018A">{{cite journal | vauthors = Shabtai Y, Fainsod A | title = Competition between ethanol clearance and retinoic acid biosynthesis in the induction of fetal alcohol syndrome | journal = Biochemistry and Cell Biology | volume = 96 | issue = 2 | pages = 148–60 | date = April 2018 | pmid = 28982012 | doi = 10.1139/bcb-2017-0132 }}</ref><ref name="Shabtai2018B">{{cite journal | vauthors = Shabtai Y, Bendelac L, Jubran H, Hirschberg J, Fainsod A | title = Acetaldehyde inhibits retinoic acid biosynthesis to mediate alcohol teratogenicity | journal = Scientific Reports | volume = 8 | issue = 1 | pages = 347 | date = January 2018 | pmid = 29321611 | pmc = 5762763 | doi = 10.1038/s41598-017-18719-7 | bibcode = 2018NatSR...8..347S }}</ref>