Document Type
Article
Rights
Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence
Disciplines
Environmental sciences
Abstract
Toxic aldehydes produced by alcohol dehydrogenases have been implicated in the pathogenesis of Helicobacter pylori-related damage to the gastric mucosa. Despite this, the enzymes that might be responsible for producing such aldehydes have not been fully described. It was, therefore, of considerable interest to characterize the alcohol oxidizing enzymes in this pathogen. Previous work in this laboratory characterized two such H. pylori enzymes that had broad specificity for a range of aromatic alcohol substrates. An enzyme with broad specificity for aliphatic alcohols is likely to be required in order that H. pylori can metabolize the wide range of substrates encountered in the gastric mucosa. In this study we describe HpSCADH, an alcohol dehydrogenase from H. pylori 26695 with broad specificity for aliphatic alcohols. HpSCADH was classified in the cD1e subfamily of classical short chain alcohol dehydrogenases. The enzyme was a monomer of approximately 29 kDa with a preference for NAD+ as cofactor. Pyrazole was found to be a competitive inhibitor of HpSCADH. The physiological role of this enzyme was explored by construction of an HpSCADH isogenic mutant. AtpH 7.0 the mutant showed reduced growth which became more pronounced when the pH was lowered to 5.0. When pyrazole was added to wild type H. pylori cells it caused growth profiles to be reduced to those of the isogenic mutant suggesting that HpSCADH inhibition alone was responsible for growth reduction. Taken together, the data relating to the alcohol metabolizing enzymes of this pathogen indicate that they play an important role in H. pylori growth and adaptation to acidic environments. The therapeutic potential of targeting H. pylori alcohol dehydrogenases is discussed
DOI
https://doi.org/10.1016/j.biocel.2013.04.006
Recommended Citation
Alka,K., Windle, H., Cornally, D., Ryan, B.J., Henehan, G.T.M. (2013). A short chain NAD(H)-dependent alcohol dehydrogenase (HpSCADH) from Helicobacter pylori: a role in growth under neutral and acidic conditions. The International Journal of Biochemistry & Cell Biology, vol.45, no.7, pp.1347-1355. doi:10.1016/j.biocel.2013.04.006
Publication Details
The International Journal of Biochemistry & Cell Biology - Volume 45, Issue 7, July 2013, Pages 1347–1355
Available here.