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The outcome of such competition is development under conditions of reduced retinoic acid signaling. Retinoic acid is one of the biologically active metabolites of vitamin A (retinol), and regulates numerous embryonic and differentiation processes. The developmental malformations characteristic of FASD resemble those observed in vitamin A deficiency syndrome as well as from inhibition of retinoic acid biosynthesis or signaling in experimental models. There is extensive biochemical and enzymatic overlap between ethanol clearance and retinoic acid biosynthesis. Several lines of evidence suggest that in the embryo, the competition takes place between acetaldehyde and retinaldehyde for the aldehyde dehydrogenase activity available. In adults, this competition also extends to the alcohol dehydrogenase activity. Ethanol-induced developmental defects can be ameliorated by increasing the levels of retinol, retinaldehyde, or retinaldehyde dehydrogenase. Acetaldehyde inhibits the production of retinoic acid by retinaldehyde dehydrogenase, further supporting the competition model. All of the evidence supports the reduction of retinoic acid signaling as the etiological trigger in the induction of FASD. <\/jats:p>","DOI":"10.1139\/bcb-2017-0132","type":"journal-article","created":{"date-parts":[[2017,10,5]],"date-time":"2017-10-05T21:35:30Z","timestamp":1507239330000},"page":"148-160","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Competition between ethanol clearance and retinoic acid biosynthesis in the induction of fetal alcohol syndrome"],"prefix":"10.1139","volume":"96","author":[{"given":"Yehuda","family":"Shabtai","sequence":"first","affiliation":[{"name":"Department of Cellular Biochemistry and Cancer Research, Institute for Medical Research Israel\u2013Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel."},{"name":"Department of Cellular Biochemistry and Cancer Research, Institute for Medical Research Israel\u2013Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Fainsod","sequence":"additional","affiliation":[{"name":"Department of Cellular Biochemistry and Cancer Research, Institute for Medical Research Israel\u2013Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel."},{"name":"Department of Cellular Biochemistry and Cancer Research, Institute for Medical Research Israel\u2013Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1079\/PNS2006496"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3784-4"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1999.00139.x"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1080\/10915810490265450"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1080\/00313029600169803"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-09614-8_5"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2012.01.014"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-009-0239-2"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2012.11.019"},{"issue":"16","key":"refg10\/ref10","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1242\/dev.128.16.3081","volume":"128","author":"Begemann G.","year":"2001","journal-title":"Development"},{"key":"refg11\/ref11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800019200"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.776914"},{"key":"refg13\/ref13","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(98)00261-5"},{"key":"refg14\/ref14","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-227967"},{"key":"refg15\/ref15","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1998.8995"},{"key":"refg16\/ref16","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840060330"},{"key":"refg17\/ref17","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-8329(96)00217-0"},{"key":"refg18\/ref18","doi-asserted-by":"publisher","DOI":"10.1080\/14767050701298365"},{"key":"refg19\/ref19","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2012.57"},{"key":"refg20\/ref20","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21312"},{"key":"refg21\/ref21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1995.tb01007.x"},{"key":"refg23\/ref23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1996.tb01948.x"},{"key":"refg24\/ref24","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(00)00558-X"},{"key":"refg25\/ref25","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(75)80919-X"},{"key":"refg26\/ref26","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.22.010402.102745E"},{"key":"refg27\/ref27","doi-asserted-by":"publisher","DOI":"10.3390\/nu4050356"},{"key":"refg28\/ref28","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-09614-8_24"},{"key":"refg29\/ref29","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.39.1.399"},{"key":"refg30\/ref30","doi-asserted-by":"publisher","DOI":"10.1002\/9780470511848.ch2"},{"key":"refg31\/ref31","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113875"},{"issue":"2","key":"refg32\/ref32","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1093\/ajcn\/63.2.220","volume":"63","author":"Cravo M.L.","year":"1996","journal-title":"Am. 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