Alcohol dehydrogenase and catalase content in perinatal infant and adult livers: potential influence on neonatal alcohol metabolism.
Methanol and ethanol are primarily metabolized through the alcohol dehydrogenase (ADH) system in adults. Under saturating substrate concentrations, blood alcohol concentrations decline at a constant rate (i.e., zero-order kinetics). Minor metabolic alcohol pathways include oxidation through the cytochrome P450 system and catalase. We previously reported a 5-week-old infant that survived intoxication at an exceptional methanol concentration (1148 mg/dL). As the rate of elimination followed first-order kinetics, we proposed that an alternate non-saturating alcohol metabolizing enzyme system such as catalase was responsible for this observation. In this study, we developed and optimized enzyme immunoassays for tissue ADH and catalase, and measured the concentration of these enzymes in the livers of 18 adults and 7 perinatal infants obtained from autopsies. The mean ADH content of perinatal infants was approximately 10-fold lower than adults (0.11+/-0.09 g/kg versus 1.00+/-0.37 g/kg liver wet weight, respectively). The alphaalpha isoenzyme of ADH was the predominant isoform in perinatal infants, while there were several isoenzymes found in adult livers. For catalase, half of the perinatal infants (n=4) had roughly equal amounts as adults (0.32+/-0.03 g/kg versus 0.37+/-0.20 g/kg wet weight, p=NS), while three other perinatal infants had significantly higher concentrations (1.55+/-0.48 g/kg versus 0.37+/-0.02 g/kg wet weight, p<0.05). In the perinatal infants, these results suggest that catalase may play a more prominent role in the metabolism of alcohols than does the ADH system and may explain the finding of first-order kinetics in case reports of high methanol and ethanol intoxication.
Tran
Minh-Nguyet
MN
Department of Pathobiology, University of Connecticut, Storrs, CT, USA.
Wu
Alan H B
AH
Hill
Dennis W
DW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000438:Alcohols / Q000378:metabolism* / Q000493:pharmacokinetics; D002374:Catalase / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000254:growth & development; D008297:Male; D008875:Middle Aged
D000438:Alcohols; D007527:Isoenzymes; D000426:Alcohol Dehydrogenase; D002374:Catalase