Metabolic and mitotic changes associated with the fetal alcohol syndrome.
In the USA, fetal alcohol syndrome (FAS) is the leading known cause of mental retardation. FAS is estimated to affect 4000 infants yearly in the USA with an additional 7000 children suffering various forms of fetal alcohol effects in the absence of the full syndrome. A comparable incidence would be expected in other industrialized countries, but essentially no data are available from either developing or third world countries. An understanding of the biochemical causes of FAS has been slow to develop, but progress has been made toward a molecular causation theory of FAS. This paper summarizes much of the current work as to the effects of fetal ethanol exposure on mitotic and metabolic parameters as well as ethanol's effect on the cellular signalling pathways thought to regulate these processes. Based upon these studies, it is apparent that exposure of embryonic tissue to ethanol results in decreased growth and that alcohol adversely affects a multitude of cellular functions critical for the growth of the developing organism, including inhibition of protein and DNA synthesis. In addition, ethanol alters the uptake of critical nutrients such as glucose and amino acids and causes changes in several kinase-mediated signal transduction pathways that regulate these biochemical processes.
Shibley
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Department of Chemistry, Penn State Berks Campus, Reading 19610, USA.
Pennington
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D002492:Central Nervous System Depressants / Q000633:toxicity*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D008297:Male; D008938:Mitosis / Q000187:drug effects*; D011247:Pregnancy; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000187:drug effects
D002492:Central Nervous System Depressants; D007328:Insulin; D011506:Proteins; D000431:Ethanol; D004247:DNA; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D005947:Glucose