Disease relevance of ALD4

• We report a method to assess ALDH2 activity in intact hepatoma cells that does not require mitochondrial isolation [1].

High impact information on ALD4

• However, the codisruption of PDA1 and ALD7 genes prevented the growth on lactate, indicating that each of these pathways contributes to the oxidative metabolism of pyruvate [2].
• Mutants disrupted for the mitochondrial acetaldehyde dehydrogenase gene (ALD7) did not oxidize pyruvate unless malate was added [2].
• Preferential ionization was tested on a yeast aldehyde dehydrogenase (ALD7), and it was shown that the ionization of some peptides was clearly suppressed by the presence of others [3].
• The exchange of the N-terminal 21 residues from the mature portion altered import, folding, and assembly of precursor ALDH1 and precursor ALDH2 [4].
• The ALDH5 gene was located on chromosome V. The commercial ALDH (designated ALDH2) was partially sequenced and appears to be a mitochondrial enzyme encoded by a gene located on chromosome XV [5].

Biological context of ALD4

• The N-terminal amino acid sequences of K(+)-ACDHs purified from several diverse strains of S. cerevisiae were determined, and found to have 81-100% identity in alignments with the product of ALD7 [6].
• Haploid mutants containing a deletion of ALD7 were constructed and, in these strains, the K(+)-ACDH was not detectable under any growth conditions examined [6].
• The absence of Ald6p was compensated by the mitochondrial isoforms and this involves the transcriptional activation of ALD4 [7].
• The specificity and sensitivity of the "acetaldehyde clamp" assay should be of value in evaluation of the effects of new agents that modify Aldh2 gene expression, as well as in the study of ALDH2 regulation in intact cells [1].

Anatomical context of ALD4

• ALDH1 must fold in the cytosol, but ALDH2 is first synthesized as a precursor and must remain unfolded during import into mitochondria [4].

Associations of ALD4 with chemical compounds

• Engineering of the pyruvate dehydrogenase bypass in Saccharomyces cerevisiae: role of the cytosolic Mg(2+) and mitochondrial K(+) acetaldehyde dehydrogenases Ald6p and Ald4p in acetate formation during alcoholic fermentation [8].
• Growth on glucose was not affected in the mutants lacking ALD7 (in contrast to the behaviour of ald6 mutants), whereas growth on ethanol was severely impaired [6].
• The co-disruption of ALD4 and PDA1 (encoding subunit E1alpha of pyruvate dehydrogenase) prevented the growth on pyruvate for both strains but prevented growth on lactate only in the double mutant derived from the YPH499 strain, indicating that the mutation effects are strain-dependent [9].
• Mature ALDH1 proved to be more stable against urea denaturation than ALDH2 [4].

Analytical, diagnostic and therapeutic context of ALD4

• Activity staining of isoelectric focusing gels showed that cytosolic ALDH1 contributed 30 to 70% of the overall activity, depending on the cofactor used, while mitochondrial ALDH2 contributed the rest [5].

References