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Gene Review

ALD6  -  aldehyde dehydrogenase (NADP(+)) ALD6

Saccharomyces cerevisiae S288c

Synonyms: ALDH1, LPE9, Magnesium-activated aldehyde dehydrogenase, cytosolic, Mg(2+)-ACDH, Mg(2+)-activated acetaldehyde dehydrogenase, ...
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Disease relevance of ALD6


High impact information on ALD6

  • This screen yielded a number of genes not previously implicated in salt stress, including ALD6, which encodes an NADP(+)-dependent aldehyde dehydrogenase, and UTR1, which encodes an NAD+ kinase [1].
  • Measurements of NADP(H) levels revealed that NADPH may not be rapidly utilized in the zwf1Delta ald6Delta mutant in glucose medium, perhaps because of a reduction in fatty acid synthesis associated with loss of Ald6p [4].
  • We performed a differential screen on wild-type and Deltaatg7/apg7 autophagy-deficient cells and found that cytosolic acetaldehyde dehydrogenase (Ald6p) decreased under nitrogen starvation [5].
  • Ald6p enzymatic activity may be disadvantageous for survival under nitrogen starvation; therefore, yeast cells may preferentially eliminate Ald6p via autophagy [5].
  • Using pulse-chase and subcellular fractionation, we have also demonstrated that Ald6p was preferentially transported to vacuoles via autophagosomes [5].

Chemical compound and disease context of ALD6


Biological context of ALD6


Anatomical context of ALD6

  • More of chimeric ALDH1 precursor was imported into mitochondria compared to its parent precursor ALDH1 [10].
  • ATE inhibited ALDH1 activity in ALDH1-transfected L1210 T cells resistant to hydroperoxycyclophosphamide (HCPA) and inhibited growth synergistically in the presence of HCPA [11].
  • Intact antibiotics which contain the MTT moiety did not cause an inhibition of yeast ALDH unless the antibiotics were first treated with potassium hydroxide and then incubated with microsomes [12].
  • ALDH-mediated oxidation of a synthetic standard of the hydroxy/aldehyde derivative of MA resulted in formation of this new metabolite, which was also a major product formed by rat hepatocytes incubated with MA [13].
  • Previous studies by gene disrupted in our laboratory revealed that the Saccharomyces cerevisiae cytosol ALDH1 played an important role in ethanol metabolism as did the class 2 mitochondrial enzyme [14].

Associations of ALD6 with chemical compounds

  • The ALD6 gene product is indispensable for providing NADPH in yeast cells lacking glucose-6-phosphate dehydrogenase activity [6].
  • The deletion of ALD6 and ALD5 decreased acetate formation in both strains, demonstrating for the first time that the mitochondrial Ald5p isoform is involved in the biosynthesis of acetate during anaerobic growth on glucose [7].
  • 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 [15].
  • 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 [8].
  • This approach was found to enrich the analysis since GND1, ZWF1 and ALD6, encoding the most important enzymes for regeneration of NADPH under anaerobic conditions, were down-regulated together with eight other genes encoding NADP(H)-dependent enzymes [16].

Regulatory relationships of ALD6

  • Using quantitative PCR analysis, ALD6 was found to be the most highly expressed among the ALD2 to ALD6 genes [17].

Other interactions of ALD6

  • Another multicopy suppressor identified in our screen, the ZMS1 gene encoding a putative transcription factor, regulates the level of ALD6 expression [6].
  • Deletion of the aldehyde dehydrogenase gene, ALD6, in wild-type and GPD2 overexpressing strains (GPD2-OP) decreased acetic acid production by three- and four-fold, respectively [18].
  • Although no significant differences in the transcriptional levels of ALD2 to ALD6 encoding acetaldehyde dehydrogenase (ALD) between 2DGR19 and NCYC1245 were observed, ALD activity in 2DGR19 was lower [17].
  • Of the seven proteins that were identified, two were previously not known to be under HOG pathway control: Ald6p, an isoform of aldehyde dehydrogenase and Dak1p, a putative dihydroxyacetone kinase [19].
  • Neither ALDH5 nor the other ALDH-like proteins identified from the genomic sequence contributed to the in vitro oxidation of acetaldehyde [2].

Analytical, diagnostic and therapeutic context of ALD6


  1. Identification of Ald6p as the target of a class of small-molecule suppressors of FK506 and their use in network dissection. Butcher, R.A., Schreiber, S.L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Molecular cloning, characterization, and potential roles of cytosolic and mitochondrial aldehyde dehydrogenases in ethanol metabolism in Saccharomyces cerevisiae. Wang, X., Mann, C.J., Bai, Y., Ni, L., Weiner, H. J. Bacteriol. (1998) [Pubmed]
  3. Inhibition of cytosolic class 3 aldehyde dehydrogenase by antisense oligonucleotides in rat hepatoma cells. Muzio, G., Canuto, R.A., Trombetta, A., Maggiora, M. Chem. Biol. Interact. (2001) [Pubmed]
  4. Sources of NADPH in yeast vary with carbon source. Minard, K.I., McAlister-Henn, L. J. Biol. Chem. (2005) [Pubmed]
  5. Ald6p is a preferred target for autophagy in yeast, Saccharomyces cerevisiae. Onodera, J., Ohsumi, Y. J. Biol. Chem. (2004) [Pubmed]
  6. The ALD6 gene product is indispensable for providing NADPH in yeast cells lacking glucose-6-phosphate dehydrogenase activity. Grabowska, D., Chelstowska, A. J. Biol. Chem. (2003) [Pubmed]
  7. Functional analysis of the ALD gene family of Saccharomyces cerevisiae during anaerobic growth on glucose: the NADP+-dependent Ald6p and Ald5p isoforms play a major role in acetate formation. Saint-Prix, F., Bönquist, L., Dequin, S. Microbiology (Reading, Engl.) (2004) [Pubmed]
  8. Identification and disruption of the gene encoding the K(+)-activated acetaldehyde dehydrogenase of Saccharomyces cerevisiae. Tessier, W.D., Meaden, P.G., Dickinson, F.M., Midgley, M. FEMS Microbiol. Lett. (1998) [Pubmed]
  9. Mechanism for benomyl action as a mitochondrial aldehyde dehydrogenase inhibitor in mice. Staub, R.E., Quistad, G.B., Casida, J.E. Chem. Res. Toxicol. (1998) [Pubmed]
  10. The N-terminal portion of mature aldehyde dehydrogenase affects protein folding and assembly. Zhou, J., Weiner, H. Protein Sci. (2001) [Pubmed]
  11. Novel competitive irreversible inhibitors of aldehyde dehydrogenase (ALDH1): restoration of chemosensitivity of L1210 cells overexpressing ALDH1 and induction of apoptosis in BAF(3) cells overexpressing bcl(2). Quash, G., Fournet, G., Chantepie, J., Gore, J., Ardiet, C., Ardail, D., Michal, Y., Reichert, U. Biochem. Pharmacol. (2002) [Pubmed]
  12. Ability of 1-methyltetrazole-5-thiol with microsomal activation to inhibit aldehyde dehydrogenase. Lipsky, J.J. Biochem. Pharmacol. (1989) [Pubmed]
  13. Metabolism of trans,trans-muconaldehyde by aldehyde and alcohol dehydrogenases: identification of a novel metabolite. Goon, D., Cheng, X., Ruth, J.A., Petersen, D.R., Ross, D. Toxicol. Appl. Pharmacol. (1992) [Pubmed]
  14. Making an Oriental equivalent of the yeast cytosolic aldehyde dehydrogenase as well as making one with positive cooperativity in coenzyme binding by mutations of glutamate 492 and arginine 480. Wei, B., Weiner, H. Chem. Biol. Interact. (2001) [Pubmed]
  15. 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. Remize, F., Andrieu, E., Dequin, S. Appl. Environ. Microbiol. (2000) [Pubmed]
  16. Genome-wide transcriptional response of a Saccharomyces cerevisiae strain with an altered redox metabolism. Bro, C., Regenberg, B., Nielsen, J. Biotechnol. Bioeng. (2004) [Pubmed]
  17. Characterization of low-acetic-acid-producing yeast isolated from 2-deoxyglucose-resistant mutants and its application to high-gravity brewing. Mizuno, A., Tabei, H., Iwahuti, M. J. Biosci. Bioeng. (2006) [Pubmed]
  18. Decreasing acetic acid accumulation by a glycerol overproducing strain of Saccharomyces cerevisiae by deleting the ALD6 aldehyde dehydrogenase gene. Eglinton, J.M., Heinrich, A.J., Pollnitz, A.P., Langridge, P., Henschke, P.A., de Barros Lopes, M. Yeast (2002) [Pubmed]
  19. Osmoregulation and protein expression in a pbs2delta mutant of Saccharomyces cerevisiae during adaptation to hypersaline stress. Akhtar, N., Blomberg, A., Adler, L. FEBS Lett. (1997) [Pubmed]
  20. Induction of autophagy by second-fermentation yeasts during elaboration of sparkling wines. Cebollero, E., Gonzalez, R. Appl. Environ. Microbiol. (2006) [Pubmed]
  21. Metabolism of trans, trans-muconaldehyde, a microsomal hematotoxic metabolite of benzene, by purified yeast aldehyde dehydrogenase and a mouse liver soluble fraction. Kirley, T.A., Goldstein, B.D., Maniara, W.M., Witz, G. Toxicol. Appl. Pharmacol. (1989) [Pubmed]
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