Adh4 is a dimeric NAD(H)-dependent alcohol dehydrogenase in the group III family, structurally distinct from the zinc-containing medium-chain Adh1/Adh2/Adh3 enzymes. Purified Adh4 is activated by zinc rather than ferrous ions and catalyzes ethanol/acetaldehyde interconversion, with reduced activity toward longer primary alcohols. It has been localized to mitochondria and is induced by Zap1 during zinc deficiency. Its contribution to bulk ethanol production in standard laboratory glucose cultures is limited, and strains retaining only ADH4 among ADH1-5 do not grow on ethanol. Altered-expression and zinc-limited conditions implicate a conditional contribution to fermentative redox metabolism. Adh4 can also redundantly reduce aldehydes to fusel alcohols in the Ehrlich pathway.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004022 alcohol dehydrogenase (NAD+) activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA on the iron-containing (group III) alcohol dehydrogenase node (PTN002608572, with E. coli and S. pombe members); ADH4 belongs to this family, distinct from ADH1/2/3/5, and is enzymatically active. Reason: Inherited activity supported by purified-enzyme data. Supporting Evidence: PMID:3282541 Characterization of the purified enzyme revealed a dimeric structure as well as a different substrate specificity and pH profile as compared to other alcohol dehydrogenase isozymes. |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | IDA PMID:3282541 Overexpression, purification and properties of alcohol dehyd... | ACCEPT | Summary: Drewke & Ciriacy overexpressed and purified ADH IV and characterised it as a dimeric NAD+-dependent ADH with substrate specificity and pH profile distinct from the zinc MDR isozymes. Reason: Direct enzymatic evidence. Supporting Evidence: PMID:3282541 Characterization of the purified enzyme revealed a dimeric structure as well as a different substrate specificity and pH profile as compared to other alcohol dehydrogenase isozymes. |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (Rhea reactions + EC 1.1.1.1) assigning alcohol dehydrogenase (NAD+) activity; correct for ADH4. Reason: Correct electronic transfer of the core activity class. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | IMP PMID:3023838 Ty insertions at two loci account for most of the spontaneou... | ACCEPT | Summary: Paquin & Williamson identified ADH4 as a locus where Ty insertions in adh1 strains activate expression and confer antimycin A resistance, i.e. restore ADH-dependent fermentative NAD+ regeneration. Reason: Genetic evidence that ADH4 encodes a functional ADH. Supporting Evidence: PMID:3023838 another 65% of the mutations are Ty insertions at ADH4, a new locus identified and cloned as described in this paper |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA assigning EC 1.1.1.1 alcohol dehydrogenase (NAD+) activity from fermentation, ethanol-degradation and Ehrlich (fusel alcohol) pathway reactions. The activity class is correct for ADH4; which pathways it physiologically serves is judged on the corresponding BP rows. Reason: Correct activity class; pathway relevance assessed separately. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA assigning EC 1.1.1.1 alcohol dehydrogenase (NAD+) activity from fermentation, ethanol-degradation and Ehrlich (fusel alcohol) pathway reactions. The activity class is correct for ADH4; which pathways it physiologically serves is judged on the corresponding BP rows. Reason: Correct activity class; pathway relevance assessed separately. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA assigning EC 1.1.1.1 alcohol dehydrogenase (NAD+) activity from fermentation, ethanol-degradation and Ehrlich (fusel alcohol) pathway reactions. The activity class is correct for ADH4; which pathways it physiologically serves is judged on the corresponding BP rows. Reason: Correct activity class; pathway relevance assessed separately. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA assigning EC 1.1.1.1 alcohol dehydrogenase (NAD+) activity from fermentation, ethanol-degradation and Ehrlich (fusel alcohol) pathway reactions. The activity class is correct for ADH4; which pathways it physiologically serves is judged on the corresponding BP rows. Reason: Correct activity class; pathway relevance assessed separately. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA assigning EC 1.1.1.1 alcohol dehydrogenase (NAD+) activity from fermentation, ethanol-degradation and Ehrlich (fusel alcohol) pathway reactions. The activity class is correct for ADH4; which pathways it physiologically serves is judged on the corresponding BP rows. Reason: Correct activity class; pathway relevance assessed separately. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA assigning EC 1.1.1.1 alcohol dehydrogenase (NAD+) activity from fermentation, ethanol-degradation and Ehrlich (fusel alcohol) pathway reactions. The activity class is correct for ADH4; which pathways it physiologically serves is judged on the corresponding BP rows. Reason: Correct activity class; pathway relevance assessed separately. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA assigning EC 1.1.1.1 alcohol dehydrogenase (NAD+) activity from fermentation, ethanol-degradation and Ehrlich (fusel alcohol) pathway reactions. The activity class is correct for ADH4; which pathways it physiologically serves is judged on the corresponding BP rows. Reason: Correct activity class; pathway relevance assessed separately. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt Reaction=a primary alcohol + NAD(+) = an aldehyde + NADH + H(+); PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0005739 mitochondrion | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: Genome-wide GFP localisation and mitochondrial proteomics place ADH4 in mitochondria. Reason: Consistent across independent datasets. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories PMID:24769239 we performed an overall quantitative proteomic and phosphoproteomic study of isolated mitochondria |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | ACCEPT | Summary: Genome-wide GFP localisation and mitochondrial proteomics place ADH4 in mitochondria. Reason: Consistent across independent datasets. Supporting Evidence: PMID:14562095 We classify these proteins, representing 75% of the yeast proteome, into 22 distinct subcellular localization categories PMID:24769239 we performed an overall quantitative proteomic and phosphoproteomic study of isolated mitochondria |
| GO:0005739 mitochondrion | IDA PMID:17054397 Assessing systems properties of yeast mitochondria through a... | ACCEPT | Summary: Perocchi et al. integrated mitochondrial datasets and experimentally validated the mitochondrial localisation of selected candidate proteins (curator IDA; ADH4 is not named in the cached text, so the curator is deferred to). Consistent with independent GFP and mitochondrial-proteome data. Reason: Experimental localisation evidence. Supporting Evidence: PMID:17054397 we experimentally validated the localization of several candidate proteins |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell "Mitochondrion" mapping (from the GFP study); consistent with experimental data. Reason: Correct location. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | UNDECIDED | Summary: Mitochondrial localization is experimentally reported; a cytosolic pool sufficient for the mapped pathway has not been independently established in the inspected sources. Reason: Pathway-compartment projection is not itself localization evidence, but mitochondrial detection also does not exclude dual localization. Retain uncertainty rather than declaring cytosolic localization absent. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | UNDECIDED | Summary: Mitochondrial localization is experimentally reported; a cytosolic pool sufficient for the mapped pathway has not been independently established in the inspected sources. Reason: Pathway-compartment projection is not itself localization evidence, but mitochondrial detection also does not exclude dual localization. Retain uncertainty rather than declaring cytosolic localization absent. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | UNDECIDED | Summary: Mitochondrial localization is experimentally reported; a cytosolic pool sufficient for the mapped pathway has not been independently established in the inspected sources. Reason: Pathway-compartment projection is not itself localization evidence, but mitochondrial detection also does not exclude dual localization. Retain uncertainty rather than declaring cytosolic localization absent. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | UNDECIDED | Summary: Mitochondrial localization is experimentally reported; a cytosolic pool sufficient for the mapped pathway has not been independently established in the inspected sources. Reason: Pathway-compartment projection is not itself localization evidence, but mitochondrial detection also does not exclude dual localization. Retain uncertainty rather than declaring cytosolic localization absent. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | UNDECIDED | Summary: Mitochondrial localization is experimentally reported; a cytosolic pool sufficient for the mapped pathway has not been independently established in the inspected sources. Reason: Pathway-compartment projection is not itself localization evidence, but mitochondrial detection also does not exclude dual localization. Retain uncertainty rather than declaring cytosolic localization absent. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | UNDECIDED | Summary: Mitochondrial localization is experimentally reported; a cytosolic pool sufficient for the mapped pathway has not been independently established in the inspected sources. Reason: Pathway-compartment projection is not itself localization evidence, but mitochondrial detection also does not exclude dual localization. Retain uncertainty rather than declaring cytosolic localization absent. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | UNDECIDED | Summary: Mitochondrial localization is experimentally reported; a cytosolic pool sufficient for the mapped pathway has not been independently established in the inspected sources. Reason: Pathway-compartment projection is not itself localization evidence, but mitochondrial detection also does not exclude dual localization. Retain uncertainty rather than declaring cytosolic localization absent. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095}. |
| GO:0005829 cytosol | RCA GO_REF:0000123 | UNDECIDED | Summary: Mitochondrial localization is experimentally reported; a cytosolic pool sufficient for the mapped pathway has not been independently established in the inspected sources. Reason: Pathway-compartment projection is not itself localization evidence, but mitochondrial detection also does not exclude dual localization. Retain uncertainty rather than declaring cytosolic localization absent. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:14562095}. |
| GO:0006068 ethanol catabolic process | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA (ethanol degradation) assigned to every ADH isozyme. Strains in which ADH4 is the sole ADH gene could neither use produced ethanol nor grow on added ethanol, so ADH4 does not support ethanol catabolism in vivo. Reason: Contradicted by quadruple-deletion analysis. Supporting Evidence: PMID:22094012 Strains Q4 and Q5 grew poorly on glucose and produced ethanol, but were neither able to utilise the produced ethanol nor grow on added ethanol. |
| GO:0006550 L-isoleucine catabolic process | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA (PWY3O-4109) placing ADH4 at the final aldehyde-reduction step of L-isoleucine catabolism (Ehrlich pathway). Gene-specific evidence for this amino acid is lacking, but the general finding that any ADH1-5 or SFA1 can perform the final fusel-alcohol step makes a redundant contribution plausible. Reason: Plausible by analogy to tested Ehrlich branches; redundant, not core. Supporting Evidence: PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | IGI PMID:12499363 The catabolism of amino acids to long chain and complex alco... | ACCEPT | Summary: Dickinson et al. (2003) used combinatorial ADH/AAD/SFA1 mutants to show the final fusel-alcohol step of amino-acid catabolism (here leucine to isoamyl alcohol) can be carried out by any one of ADH1-5 or SFA1. ADH4 therefore catalyses a step of leucine catabolism, though redundantly. Reason: Genetic interaction evidence that the enzyme performs the reductive step of the Ehrlich pathway. Supporting Evidence: PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | IGI PMID:12499363 The catabolism of amino acids to long chain and complex alco... | ACCEPT | Summary: Dickinson et al. (2003) used combinatorial ADH/AAD/SFA1 mutants to show the final fusel-alcohol step of amino-acid catabolism (here leucine to isoamyl alcohol) can be carried out by any one of ADH1-5 or SFA1. ADH4 therefore catalyses a step of leucine catabolism, though redundantly. Reason: Genetic interaction evidence that the enzyme performs the reductive step of the Ehrlich pathway. Supporting Evidence: PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | IGI PMID:12499363 The catabolism of amino acids to long chain and complex alco... | ACCEPT | Summary: Dickinson et al. (2003) used combinatorial ADH/AAD/SFA1 mutants to show the final fusel-alcohol step of amino-acid catabolism (here leucine to isoamyl alcohol) can be carried out by any one of ADH1-5 or SFA1. ADH4 therefore catalyses a step of leucine catabolism, though redundantly. Reason: Genetic interaction evidence that the enzyme performs the reductive step of the Ehrlich pathway. Supporting Evidence: PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | IGI PMID:12499363 The catabolism of amino acids to long chain and complex alco... | ACCEPT | Summary: Dickinson et al. (2003) used combinatorial ADH/AAD/SFA1 mutants to show the final fusel-alcohol step of amino-acid catabolism (here leucine to isoamyl alcohol) can be carried out by any one of ADH1-5 or SFA1. ADH4 therefore catalyses a step of leucine catabolism, though redundantly. Reason: Genetic interaction evidence that the enzyme performs the reductive step of the Ehrlich pathway. Supporting Evidence: PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | IGI PMID:12499363 The catabolism of amino acids to long chain and complex alco... | ACCEPT | Summary: Dickinson et al. (2003) used combinatorial ADH/AAD/SFA1 mutants to show the final fusel-alcohol step of amino-acid catabolism (here leucine to isoamyl alcohol) can be carried out by any one of ADH1-5 or SFA1. ADH4 therefore catalyses a step of leucine catabolism, though redundantly. Reason: Genetic interaction evidence that the enzyme performs the reductive step of the Ehrlich pathway. Supporting Evidence: PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006552 L-leucine catabolic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (leucine degradation, PWY3O-4112) for the 3-methylbutanal to 3-methylbutanol reduction; consistent with the genetic evidence that ADH4 can perform this step. Reason: Supported by IGI evidence for the same step. Supporting Evidence: PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006559 L-phenylalanine catabolic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-4115) placing ADH4 at the aldehyde-reduction step of L-phenylalanine catabolism via the Ehrlich pathway. Dickinson et al. studied phenylalanine and tryptophan catabolism and found any of ADH1-5 or SFA1 can reduce the aldehyde to the fusel alcohol. Reason: Supported by combinatorial mutant analysis of the same pathway. Supporting Evidence: PMID:12499363 The catabolism of phenylalanine to 2-phenylethanol and of tryptophan to tryptophol were studied PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006569 L-tryptophan catabolic process | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways RCA (PWY3O-214) placing ADH4 at the aldehyde-reduction step of L-tryptophan catabolism via the Ehrlich pathway. Dickinson et al. studied phenylalanine and tryptophan catabolism and found any of ADH1-5 or SFA1 can reduce the aldehyde to the fusel alcohol. Reason: Supported by combinatorial mutant analysis of the same pathway. Supporting Evidence: PMID:12499363 The catabolism of phenylalanine to 2-phenylethanol and of tryptophan to tryptophol were studied PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006572 L-tyrosine catabolic process | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA (PWY3O-4108) placing ADH4 at the final aldehyde-reduction step of L-tyrosine catabolism (Ehrlich pathway). Gene-specific evidence for this amino acid is lacking, but the general finding that any ADH1-5 or SFA1 can perform the final fusel-alcohol step makes a redundant contribution plausible. Reason: Plausible by analogy to tested Ehrlich branches; redundant, not core. Supporting Evidence: PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0006574 L-valine catabolic process | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA (PWY3O-4105) placing ADH4 at the final aldehyde-reduction step of L-valine catabolism (Ehrlich pathway). Gene-specific evidence for this amino acid is lacking, but the general finding that any ADH1-5 or SFA1 can perform the final fusel-alcohol step makes a redundant contribution plausible. Reason: Plausible by analogy to tested Ehrlich branches; redundant, not core. Supporting Evidence: PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0008270 zinc ion binding | RCA PMID:30358795 The cellular economy of the Saccharomyces cerevisiae zinc pr... | ACCEPT | Summary: Purified Adh4 is zinc-activated despite belonging to the historically iron-containing alcohol dehydrogenase family. Reason: Direct purified-enzyme evidence (PMID:3282541) supports the catalytic zinc property independently of the zinc-proteome classification. A family name and expression under zinc starvation do not establish ferrous-ion use. Supporting Evidence: PMID:3282541 we could demonstrate that ADHIV is activated by zinc ions, like the other yeast alcohol dehydrogenase isozymes, and not by ferrous ions |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro Fe-ADH family mapping to generic oxidoreductase activity; correct but uninformative for an NAD+-dependent alcohol dehydrogenase. Reason: Too general. Proposed replacements: alcohol dehydrogenase (NAD+) activity Supporting Evidence: PMID:3282541 Characterization of the purified enzyme revealed a dimeric structure as well as a different substrate specificity and pH profile as compared to other alcohol dehydrogenase isozymes. |
| GO:0019658 bifid shunt | RCA GO_REF:0000123 | REMOVE | Summary: YeastPathways RCA from GLUCFERMEN-PWY mapped to GO "bifid shunt", which is the Bifidobacterium heterofermentative route from glucose to lactate and acetate via phosphoketolase. S. cerevisiae has no bifid shunt; ADH4 (an alcohol dehydrogenase) has no role in such a pathway. Reason: Mis-mapped pathway term: wrong pathway for yeast and for an alcohol dehydrogenase. Alcoholic fermentation is represented by GO:0019655 pyruvate fermentation to ethanol where supported. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt Reaction=ethanol + NAD(+) = acetaldehyde + NADH + H(+); |
| GO:0046395 carboxylic acid catabolic process | IEA GO_REF:0000117 | MODIFY | Summary: Adh4 reduces aldehydes downstream of amino-acid transamination/decarboxylation in the Ehrlich pathway. Reason: Carboxylic acid catabolism is broad but not false: amino acids are carboxylic acids, and an enzyme can participate in their multistep catabolism without directly consuming the original acid. Refine to the supported leucine, phenylalanine and tryptophan pathways already represented. Proposed replacements: L-leucine catabolic process L-phenylalanine catabolic process L-tryptophan catabolic process Supporting Evidence: PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | MODIFY | Summary: The supported activating metal for purified Adh4 is zinc. Reason: Refine generic metal binding to zinc ion binding already present in this review. Conditional iron occupancy remains unresolved; do not infer it from the family name. Proposed replacements: zinc ion binding Supporting Evidence: PMID:3282541 we could demonstrate that ADHIV is activated by zinc ions, like the other yeast alcohol dehydrogenase isozymes, and not by ferrous ions |
| GO:0047018 indole-3-acetaldehyde reductase (NADH) activity | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways RCA (tryptophan degradation, PWY3O-214) assigning reduction of indole-3-acetaldehyde to tryptophol. Dickinson et al. showed the final aldehyde-to-fusel-alcohol step can be performed by any of ADH1-5 or SFA1, so ADH4 can contribute redundantly. Reason: Plausible redundant contribution to tryptophol formation; not a core activity. Supporting Evidence: PMID:12499363 the final step of amino acid catabolism (conversion of an aldehyde to a long chain or complex alcohol) can be accomplished by any one of the ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, Adh5p) or by Sfa1p (formaldehyde dehydrogenase.) PMID:12499363 The catabolism of phenylalanine to 2-phenylethanol and of tryptophan to tryptophol were studied |
| GO:0120542 ethanol dehydrogenase (NAD+) activity | EXP PMID:3282541 Overexpression, purification and properties of alcohol dehyd... | ACCEPT | Summary: Purified ADH IV oxidises ethanol with NAD+; UniProt notes drastically reduced activity on alcohols of four or more carbons. Reason: Specific activity on ethanol demonstrated. Supporting Evidence: PMID:3282541 Characterization of the purified enzyme revealed a dimeric structure as well as a different substrate specificity and pH profile as compared to other alcohol dehydrogenase isozymes. file:yeast/ADH4/ADH4-uniprot.txt Reaction=ethanol + NAD(+) = acetaldehyde + NADH + H(+); |
| GO:0120542 ethanol dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Rhea/ARBA mapping (RHEA:25290) to ethanol dehydrogenase (NAD+) activity; ethanol is the preferred substrate of the yeast ADHs and ADH4 is documented to act on ethanol. Reason: Correct specific activity. Supporting Evidence: file:yeast/ADH4/ADH4-uniprot.txt Reaction=ethanol + NAD(+) = acetaldehyde + NADH + H(+); |
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Download this section (compressed HTML)Q: Is ADH4 a zinc- or iron-dependent enzyme in vivo, and does its Zap1-dependent induction under zinc deficiency reflect a zinc-sparing replacement for ADH1?
Q: What is the physiological substrate and role of mitochondrial ADH4?
Experiment: Determine the metal content of ADH4 purified from zinc-replete and zinc-deficient yeast by ICP-MS and correlate with activity.
Alcohol dehydrogenase isoenzyme type IV; dimeric enzyme demonstrated to be zinc-dependent despite sequence similarity to iron-activated alcohol dehydrogenases; transcription is induced in response to zinc deficiency
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