Unbalance between Pyridine Nucleotide Cofactors in The SOD1 Deficient Yeast Saccharomyces cerevisiae Causes Hypersensitivity to Alcohols and Aldehydes

Alcohol and aldehyde dehydrogenases are especially relevant enzymes involved in metabolic and detoxification reactions that occur in living cells. The comparison between the gene expression, protein content, and enzymatic activities of cytosolic alcohol and aldehyde dehydrogenases of the wild-type strain and the Delta sod1 mutant lacking superoxide dismutase 1, which is hypersensitive to alcohols and aldehydes, shows that the activity of these enzymes is significantly higher in the Delta sod1 mutant, but this is not a mere consequence of differences in the enzymatic protein content nor in the expression levels of genes. The analysis of the NAD(H) and NADP(H) content showed that the higher activity of alcohol and aldehyde dehydrogenases in the Delta sod1 mutant could be a result of the increased availability of pyridine nucleotide cofactors. The higher level of NAD(+) in the Delta sod1 mutant is not related to the higher level of tryptophan; in turn, a higher generation of NADPH is associated with the upregulation of the pentose phosphate pathway. It is concluded that the increased sensitivity of the Delta sod1 mutant to alcohols and aldehydes is not only a result of the disorder of redox homeostasis caused by the induction of oxidative stress but also a consequence of the unbalance between pyridine nucleotide cofactors.

Automated summary

Alcohol and aldehyde dehydrogenases play important roles in metabolic and detoxification reactions. Comparing their activity in a wild-type strain and a Delta sod1 mutant, it was found that the mutant showed significantly higher activity, which was not simply caused by differences in protein content or gene expression. Further analysis revealed that the increased activity in the mutant may be due to the higher availability of pyridine nucleotide cofactors. Additionally, the imbalance between NAD(+) and NADPH, caused by upregulation of the pentose phosphate pathway, also contributes to the mutant's increased sensitivity to alcohols and aldehydes.