Human alcohol dehydrogenasee (ADH) is a cinokex system constitued by not less than four classes (I_IV) of enzymes, grouped in base of their structural and kinetic properties, and their espression pattern. All ADH classes, with the exception of class III, can metabolize retinol and retinal \i in vitro\i0 , although class IV is the most efficient among them. In addition, this class is distributed in epithelia which require retinoic acid for differentiation. In vertebrates, retinoic acid acts as a morphogen durin embryogenesis, being responsible of differentiation of nervous system and of cranofacial region. The working hypothesis is that ADH, besides participating in ethanol metabolism, has a capital role in the metabolic pathways that synthesizes retinoic acid. Thus, ethanol could inhibit retinoid metabolism catalyzed by ADH, interfering with the normal developement of central nervous system. This could explain some of teratogenic effects of ethanol (fetal alcohol syndrome), which resemble those produced by retinoids in escess or defect. The fundamental goal is to investigate the function of ADH in retinoid metabolism during neuronal differentiation. As a model, we will use embryonal carcinoma cells, which are ableto differentiate to neuronal cells in the presence of retinoic acid. The ADH system will be characterized in embrional cells and in cells undergoing different stages of neuronal differentiation. The effect of retinol on differentiation will be compared with that of retinoic acid, and their metabolic conversion will be studied, while investigating whether ADHB activity is responible for it. In parallel, the effect of ethanol on these processes and on the functionally of nature neurnal cells eill be assessed.
|Effective start/end date||1/05/97 → 1/05/00|
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