The ontogeny, distribution, and regulation of alcohol dehydrogenase 3: implications for pulmonary physiology.
Class III alcohol dehydrogenase (ADH3), also termed formaldehyde dehydrogenase or S-nitrosoglutathione reductase, plays a critical role in the enzymatic oxidation of formaldehyde and reduction of nitrosothiols that regulate bronchial tone. Considering reported associations between formaldehyde vapor exposure and childhood asthma risk, and thus potential involvement of ADH3, we reviewed the ontogeny, distribution, and regulation of mammalian ADH3. Recent studies indicate that multiple biological and chemical stimuli influence expression and activity of ADH3, including the feedback regulation of nitrosothiol metabolism. The levels of ADH3 correlate with, and potentially influence, bronchial tone; however, data gaps remain with respect to the expression of ADH3 during postnatal and early childhood development. Consideration of ADH3 function relative to the respiratory effects of formaldehyde, as well as to other chemical and biological exposures that might act in an additive or synergistic manner with formaldehyde, might be critical to gain better insight into the association between formaldehyde exposure and childhood asthma.
Thompson
Chad M
CM
National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA. cthompson@toxstrategies.com
Sonawane
Babasaheb
B
Grafström
Roland C
RC
D000393:Air Pollutants / Q000009:adverse effects* / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D001711:Biotransformation; D016084:Bronchoconstriction / Q000187:drug effects; D002648:Child; D005557:Formaldehyde / Q000009:adverse effects* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D010084:Oxidation-Reduction; D026403:S-Nitrosothiols / Q000378:metabolism; D013379:Substrate Specificity
D000393:Air Pollutants; D026403:S-Nitrosothiols; D005557:Formaldehyde; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase